US11208487B2 - Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies - Google Patents
Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies Download PDFInfo
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Definitions
- antibodies with binding specificity for HLA-G and compositions comprising the antibodies, including pharmaceutical compositions, diagnostic compositions, and kits. Also provided are methods of using anti-HLA-G antibodies for therapeutic and diagnostic purposes.
- HLA-G histocompatibility antigen, class I, G also known as human leukocyte antigen G (HLA-G)
- HLA-G is a protein that in humans is encoded by the HLA-G gene.
- HLA-G belongs to the HLA nonclassical class I heavy chain paralogues.
- HLA-G is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). There are membrane bound and soluble forms of HLA-G.
- HLA-G is normally expressed at the maternal-fetal interface and other immune-privileged sites. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells, while the classical MHC class I genes (HLA-A and HLA-B) are not. As HLA-G was first identified in placenta samples, many studies have evaluated its role in pregnancy disorders, such as preeclampsia and recurrent pregnancy loss. See, Michita, Rafael Tomoyaet al., Human Immunology. 2016, 77 (10): 892-897, which is incorporated by reference herein in its entirety, including any drawings.
- HLA-G has been shown to be immune-suppressive. By binding receptors expressed on various myeloid and lymphoid cells. HLA-G may directly inhibit the functions of NK cells, cytotoxic T-lymphocytes, B cells, neutrophils, monocytes, macrophages and dendritic cells. HLA-G also inhibits T and NK cell proliferation and cytolytic activities. HLA-G suppresses phagocytosis and induces the generation or expansion of regulatory T cells.
- HLA-G mediates immune function through at least three ITIM-containing inhibitory receptors, ILT2, ILT4, and KIR2DL4.
- ILT2, ILT4, and KIR2DL4 On lymphoid and myeloid cells, for example, HLA-G mediates function through ILT2.
- myeloid cells HLA-G mediates function through ILT4.
- ILT4 and ILT2 On lymphoid and myeloid cells, HLA-G mediates function through ILT4.
- ILT2DL4 ILT2DL4
- ILT2DL4 ILT2DL4
- HLA-G is an immune checkpoint target.
- HLA-G can directly inhibit immune cell function through receptor binding and/or trogocytosis and impairment of chemotaxis.
- HLA-G can lend tumor cells a higher invasive and metastatic potential.
- HLA-G promotes evasion of tumor immune surveillance, and enhances metastasis and the progression of malignancies.
- HLA-G has other effects, such as, inhibition of immune cell cytolysis, induction of immune cell apoptosis, and/or the generation of regulatory cells through receptor binding and/or trogocytosis.
- HLA-G expression is upregulated on a broad spectrum of tumors and is associated with poor prognosis and disease progression. Serum HLA-G levels are elevated in breast, lung, colorectal cancer (CRC), gastric, esophageal, neuroblastoma, cervical, and hematological cancers. HLA-G has also been found to be correlated with clinical parameters in advanced disease, such as, tumor metastasis, poor prognosis, immune escape, and tumor invasiveness.
- HLA-G is an attractive target for diseases, such as, for example, cancer.
- the antibodies that selectively bind HLA-G.
- the antibodies bind human HLA-G.
- the antibodies comprise at least one CDR sequence defined by a consensus sequence provided in this disclosure.
- the antibodies comprise one or more of an illustrative CDR, V H , or V L sequence provided in this disclosure, or a variant thereof.
- the variant is a variant with one or more conservative amino acid substitutions.
- compositions and kits comprising the antibodies.
- the compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used.
- the pharmaceutical composition is a composition for parenteral administration.
- the method is a method of treatment. In some embodiments, the method is an analytical method. In some embodiments, the method is a method of purifying and/or quantifying HLA-G.
- the method is a diagnostic method.
- the diagnostic method comprises or consists of detecting tumor expressed HLA-G.
- the diagnostic method comprises or consists of detecting soluble HLA-G.
- the detection method comprises of consists of detecting HLA-G expression on immune cells.
- the antibodies are used to treat a disease or condition.
- the disease or condition is selected from a cancer, autoimmune disease, and infection.
- Some aspects provide for the use of any of the antibodies or pharmaceutical compositions provided herein to treat a disease or condition selected from a cancer, autoimmune disease, and infection.
- FIG. 1 provides a table showing avid and monomeric affinities of anti-HLA-G antibodies to recombinant HLA-G protein.
- FIG. 2A and FIG. 2B provide biolayer interferometry sensorgrams showing anti-HLA-G antibodies that bind to HLA-G and can be separated into three biochemical bins based on their ability to cross-block each other when tested for binding in pairwise fashion.
- FIG. 3 provide biolayer interferometry sensorgrams showing antibodies that bind and block HLA-G interaction with ILT2 and ILT4 at varying levels of effectiveness.
- FIG. 4 shows evaluation of anti-HLA-G antibodies binding to naturally expressed HLA-G found on JEG-3 tumor cells.
- FIG. 5A , FIG. 5B , FIG. 5C , and FIG. 5D provide data showing anti-HLA-G Fabs and antibodies that restore NKL killing activity by blocking suppression mediated through interaction of HLA-G with ILT2 or ILT4.
- FIG. 6B , FIG. 6C , and FIG. 6D provides evaluation of anti-HLA-G antibodies to reverse HLA-G mediated suppression of primary human cells.
- FIG. 6A and FIG. 6B provide evaluation of phagocytosis in a human macrophage assay.
- FIG. 6C provides evaluation of primary human NK cell cytotoxic activity.
- FIG. 6D provides evaluation of primary human CD8 + T cell function.
- FIG. 7A and FIG. 7B shows results representing values for binding of anti-HLA-G antibodies to individual recombinant HLA class Ia antigens immobilized on beads.
- FIG. 8 shows the evaluation of anti-HLA-G antibodies binding to a panel of 28 HLA-typed B-LCL lines.
- FIG. 9A and FIG. 9B show the evaluation of anti-HLA-G antibodies binding to various forms of HLA-G after site-directed mutagenesis.
- FIG. 10 provides evidence for tumor growth inhibition by an anti-HLA-G antibody with and Fe effector function in a mouse tumor xenograft tumor model using 721.221 cells expressing HLA-G.
- the term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ⁇ 10%, ⁇ 5%, or ⁇ 1%. In certain embodiments, the term “about” indicates the designated value ⁇ one standard deviation of that value.
- immunoglobulin refers to a class of structurally related proteins generally comprising two pairs of polypeptide chains: one pair of light (L) chains and one pair of heavy (H) chains. In an “intact immunoglobulin,” all four of these chains are interconnected by disulfide bonds. The structure of immunoglobulins has been well characterized. See, e.g., Paul, Fundamental Immunology 7th ed., Ch. 5 (2013) Lippincott Williams & Wilkins, Philadelphia, Pa. Briefly, each heavy chain typically comprises a heavy chain variable region (V H ) and a heavy chain constant region (CH). The heavy chain constant region typically comprises three domains, C H1 , C H2 , and C H3 . Each light chain typically comprises a light chain variable region (V L ) and a light chain constant region. The light chain constant region typically comprises one domain, abbreviated C L .
- antibody describes a type of immunoglobulin molecule and is used herein in its broadest sense.
- An antibody specifically includes intact antibodies (e.g., intact immunoglobulins), and antibody fragments and antigen binding proteins.
- Antibodies comprise at least one antigen-binding domain.
- One example of an antigen-binding domain is an antigen binding domain formed by a V H -V L dimer.
- An “HLA-G antibody,” “anti-HLA-G antibody,” “HLA-G Ab,” “HLA-G-specific antibody,” or “anti-HLA-G Ab” is an antibody, as described herein, which binds specifically to the antigen HLA-G.
- the V H and V L regions may be further subdivided into regions of hypervariability (“hypervariable regions (HVRs);” also called “complementarity determining regions” (CDRs)) interspersed with regions that are more conserved.
- the more conserved regions are called framework regions (FRs).
- Each V H and V L generally comprises three CDRs and four FRs, arranged in the following order (from N-terminus to C-terminus): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.
- the CDRs are involved in antigen binding, and confer antigen specificity and binding affinity to the antibody. See Kabat et al., Sequences of Proteins of Immunological Interest 5th ed. (1991) Public Health Service, National Institutes of Health, Bethesda, Md., incorporated by reference in its entirety.
- the light chain from any vertebrate species can be assigned to one of two types, called kappa and lambda, based on the sequence of the constant domain.
- the heavy chain from any vertebrate species can be assigned to one of five different classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also designated ⁇ , ⁇ , ⁇ , ⁇ , and ⁇ , respectively.
- the IgG and IgA classes are further divided into subclasses on the basis of differences in sequence and function. Humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.
- the amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997 , J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996 , J. Mol. Biol. 262:732-745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Plückthun, J. Mol. Biol., 2001, 309:657-70 (“AHo” numbering scheme), each of which is incorporated by reference in its entirety.
- Kabat numbering scheme
- Al-Lazikani et al. 1997 , J. Mol. Biol., 273:927-948
- Chothia numbering scheme
- Table 1 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 as identified by the Kabat and Chothia schemes.
- residue numbering is provided using both the Kabat and Chothia numbering schemes.
- the numbering scheme used for identification of a particular CDR herein is the Kabat/Chothia numbering scheme. Where the residues encompassed by these two numbering schemes diverge, the numbering scheme is specified as either Kabat or Chothia.
- EU numbering scheme is generally used when referring to a residue in an antibody heavy chain constant region (e.g., as reported in Kabat et al., supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein.
- antibody fragment comprises a portion of an intact antibody, such as the antigen binding or variable region of an intact antibody.
- Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab′) 2 fragments, Fab′ fragments, scFv (sFv) fragments, and scFv-Fc fragments.
- “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.
- Fab fragments comprise, in addition to the heavy and light chain variable domains, the constant domain of the light chain and the first constant domain (Cm) of the heavy chain.
- Fab fragments may be generated, for example, by papain digestion of a full-length antibody.
- F(ab′) 2 ” fragments contain two Fab′ fragments joined, near the hinge region, by disulfide bonds.
- F(ab′) 2 fragments may be generated, for example, by pepsin digestion of an intact antibody.
- the F(ab′) fragments can be dissociated, for example, by treatment with ⁇ -mercaptoethanol.
- Single-chain Fv or “sFv” or “scFv” antibody fragments comprise a V H domain and a V L domain in a single polypeptide chain.
- the V H and V L are generally linked by a peptide linker.
- scFv-Fc” fragments comprise an scFv attached to an Fc domain.
- an Fc domain may be attached to the C-terminal of the scFv.
- the Fc domain may follow the V H or V L , depending on the orientation of the variable domains in the scFv (i.e., V H -V L or V L -V H ). Any suitable Fc domain known in the art or described herein may be used.
- a monoclonal antibody refers to an antibody from a population of substantially homogeneous antibodies.
- a population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts.
- a monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies.
- the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones.
- the selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in a subject.
- chimeric antibody refers to an antibody in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species.
- “Humanized” forms of non-human antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody.
- a humanized antibody is generally a human immunoglobulin (recipient antibody) in which residues from one or more CDRs are replaced by residues from one or more CDRs of a non-human antibody (donor antibody).
- the donor antibody can be any suitable non-human antibody, such as a mouse, rat, rabbit, chicken, or non-human primate antibody having a desired specificity, affinity, or biological effect.
- selected framework region residues of the recipient antibody are replaced by the corresponding framework region residues from the donor antibody.
- Humanized antibodies may also comprise residues that are not found in either the recipient antibody or the donor antibody. Such modifications may be made to further refine antibody function.
- a “human antibody” is one which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.
- an “isolated antibody” is one that has been separated and/or recovered from a component of its natural environment. Components of the natural environment may include enzymes, hormones, and other proteinaceous or nonproteinaceous materials.
- an isolated antibody is purified to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence, for example by use of a spinning cup sequenator.
- an isolated antibody is purified to homogeneity by gel electrophoresis (e.g., SDS-PAGE) under reducing or nonreducing conditions, with detection by Coomassie blue or silver stain.
- An isolated antibody includes an antibody in situ within recombinant cells, since at least one component of the antibody's natural environment is not present.
- an isolated antibody is prepared by at least one purification step.
- an isolated antibody is purified to at least 80%, 85%, 90%, 95%, or 99% by weight. In some embodiments, an isolated antibody is provided as a solution comprising at least 85%, 90%, 95%, 98%, 99% to 100% by weight of an antibody, the remainder of the weight comprising the weight of other solutes dissolved in the solvent.
- Affinity refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen).
- the affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (K D ).
- K D dissociation constant
- Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology, such as a Biacore® instrument, or using bio-layer interferometry technology, such as an Octet® instrument.
- the terms “specific binding,” “specifically binds to,” “specific for,” “selectively binds.” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction.
- Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule.
- Specific binding can also be determined by competition with a control molecule that is similar to the target, such as an excess of non-labeled target. In that case, specific binding is indicated if the binding of the labeled target to a probe is competitively inhibited by the excess non-labeled target.
- k d (sec ⁇ 1 ), as used herein, refers to the dissociation rate constant of a particular antibody-antigen interaction. This value is also referred to as the k off value.
- k a (M ⁇ 1 ⁇ sec ⁇ 1 ), as used herein, refers to the association rate constant of a particular antibody-antigen interaction. This value is also referred to as the k on value.
- K D K d /k a .
- an “affinity matured” antibody is one with one or more alterations in one or more CDRs or FRs that result in an improvement in the affinity of the antibody for its antigen, compared to a parent antibody which does not possess the alteration(s).
- an affinity matured antibody has nanomolar or picomolar affinity for the target antigen.
- Affinity matured antibodies may be produced using a variety of methods known in the art. For example. Marks et al. ( Bio/Technology, 1992, 10:779-783, incorporated by reference in its entirety) describes affinity maturation by V H and V L domain shuffling. Random mutagenesis of CDR and/or framework residues is described by, for example, Barbas et al. ( Proc. Nat. Acad.
- the term “competes with” or “cross-competes with” indicates that the two or more antibodies compete for binding to an antigen (e.g., HLA-G).
- HLA-G is coated on a plate and allowed to bind a first antibody, after which a second, labeled antibody is added. If the presence of the first antibody reduces binding of the second antibody, then the antibodies compete.
- the term “competes with” also includes combinations of antibodies where one antibody reduces binding of another antibody, but where no competition is observed when the antibodies are added in the reverse order. However, in some embodiments, the first and second antibodies inhibit binding of each other, regardless of the order in which they are added. In some embodiments, one antibody reduces binding of another antibody to its antigen by at least 50%, at least 60%, at least 70%, at least 80%, or at least 900%.
- epitope means a portion of an antigen capable of specific binding to an antibody.
- Epitopes frequently consist of surface-accessible amino acid residues and/or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents.
- An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding.
- the epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to HLA-G variants with different point-mutations.
- Percent “identity” between a polypeptide sequence and a reference sequence is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to the amino acid residues in the reference sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, or CLUSTAL OMEGA software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.
- a “conservative substitution” or a “conservative amino acid substitution,” refers to the substitution of one or more amino acids with one or more chemically or functionally similar amino acids. Conservative substitution tables providing similar amino acids are well known in the art. Polypeptide sequences having such substitutions are known as “conservatively modified variants.” By way of example, the following groups of amino acids are considered conservative substitutions for one another.
- amino acid refers to the twenty common naturally occurring amino acids.
- Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gin; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr, T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V).
- Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspart
- Treating” or “treatment” of any disease or disorder refers, in certain embodiments, to ameliorating a disease or disorder that exists in a subject.
- “treating” or “treatment” includes ameliorating at least one physical parameter, which may be indiscernible by the subject.
- “treating” or “treatment” includes modulating the disease or disorder, either physically (e.g., stabilization of a discernible symptom) or physiologically (e.g., stabilization of a physical parameter) or both.
- “treating” or “treatment” includes delaying or preventing the onset of the disease or disorder.
- terapéuticaally effective amount refers to an amount of an antibody or composition that when administered to a subject is effective to treat a disease or disorder.
- the term “subject” means a mammalian subject. Exemplary subjects include, but are not limited to humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, avians, goats and sheep. In certain embodiments, the subject is a human. In some embodiments, the subject has cancer, an autoimmune disease or condition, and/or an infection that can be treated with an antibody provided herein. In some embodiments, the subject is a human that is suspected to have cancer, an autoimmune disease or condition, and/or an acute infection and chronic infection.
- antibodies that selectively bind human HLA-G.
- the antibody selectively binds to the extracellular domain of human HLA-G.
- the antibody has one or more CDRs having particular lengths, in terms of the number of amino acid residues.
- the Chothia CDR-H1 of the antibody is 6, 7, 8, or 9 residues in length.
- the Kabat CDR-H1 of the antibody is 4, 5, 6, or 7 residues in length.
- the Chothia CDR-H2 of the antibody is 5, 6, or 7 residues in length.
- the Kabat CDR-H2 of the antibody is 15, 16, 17, or 18 residues in length.
- the Kabat/Chothia CDR-H3 of the antibody is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 residues in length.
- the Kabat/Chothia CDR-L1 of the antibody is 9, 10, 11, 12, 13, 14, 15, or 16 residues in length. In some aspects, the Kabat/Chothia CDR-L2 of the antibody is 6, 7, or 8 residues in length. In some aspects, the Kabat/Chothia CDR-L3 of the antibody is 8, 9, 10, 1, or 12 residues in length.
- the antibody comprises a light chain.
- the light chain is a kappa light chain.
- the light chain is a lambda light chain.
- the antibody comprises a heavy chain.
- the heavy chain is an IgA.
- the heavy chain is an IgD.
- the heavy chain is an IgE.
- the heavy chain is an IgG.
- the heavy chain is an IgM.
- the heavy chain is an IgG1.
- the heavy chain is an IgG2.
- the heavy chain is an IgG3.
- the heavy chain is an IgG4.
- the heavy chain is an IgA1. In some aspects, the heavy chain is an IgA2.
- the antibody is an antibody fragment. In some aspects, the antibody fragment is an Fv fragment. In some aspects, the antibody fragment is a Fab fragment. In some aspects, the antibody fragment is a F(ab′) 2 fragment. In some aspects, the antibody fragment is a Fab′ fragment. In some aspects, the antibody fragment is an scFv (sFv) fragment. In some aspects, the antibody fragment is an scFv-Fc fragment.
- the antibody is a monoclonal antibody. In some embodiments, the antibody is a polyclonal antibody.
- the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a human antibody.
- the antibody is an affinity matured antibody. In some aspects, the antibody is an affinity matured antibody derived from an illustrative sequence provided in this disclosure.
- the antibody blocks HLA-G interaction and/or binding to an ITIM inhibitory receptor. In some embodiments, the antibody blocks HLA-G interaction and/or binding to ILT2. In some embodiments, the antibody blocks HLA-G interaction and/or binding to ILT4. In some embodiments, the antibody blocks HLA-G interaction and/or binding to KIR2DL4. In embodiments, the antibody binds HLA-G but does not block the interaction between HLA-G and ILT2, ILT4, and/or KIRDL4. In some embodiments, the antibody disrupts HLA-G heterodimer and/or prevents dimerization of HLA-G.
- the antibody inhibits immune suppressive function. In some embodiments, the antibody inhibits HLA-G mediated suppression of NK cells. In some embodiments, the antibody inhibits HLA-G mediated suppression of cytotoxic T lymphocytes. In some embodiments, the antibody inhibits HLA-G mediated suppression of B cells. In some embodiments, the antibody inhibits HLA-G mediated suppression of neutrophils. In some embodiments, the antibody inhibits HLA-G mediated suppression of dendritic cells. In some embodiments, the antibody inhibits HLA-G mediated suppression of macrophages. In some embodiments, the antibody inhibits HLA-G mediated suppression of monocytes. In some embodiments, the antibody inhibits HLA-G mediated suppression of NK and/or T cell cytolysis and/or proliferation.
- the antibody prevents or inhibits HLA-G mediated suppression of phagocytosis. In some embodiments, the antibody mediates HLA-G mediated induction of T regulatory cells. In some embodiments, the antibody prevents or inhibits the generation or expansion of regulatory T cells.
- the antibodies provided herein may be useful for the treatment of a variety of diseases and conditions, including cancers, autoimmune diseases, and infections.
- the antibody inhibits HLA-G function on tumor cells.
- the antibody inhibits HLA-G function on immune cells.
- the antibody inhibits HLA-G function on myeloid cells.
- the antibody inhibits HLA-G function on Tcell subsets.
- the antibody inhibits metastasis.
- the antibody inhibits angiogenesis.
- the antibody competes or is capable of competing for binding to human HLA-G with another antibody.
- the antibody comprises or consists an antibody that is capable of competing for binding to human HLA-G with a reference antibody, wherein the reference antibody binds to an epitope comprising position 195, 197, and/or 198 of SEQ ID NO: 342 on a human HLA-G polypeptide.
- the antibody and the reference antibody cross-compete or are capable of cross-competing for binding to human HLA-G with another antibody.
- the antibody binds to an epitope comprising position 195, 197, and/or 198 of SEQ ID NO: 342 on a human HLA-G polypeptide.
- the epitope comprises or consists of a contiguous or non-contiguous span of amino acids including residues 195, 197, and/or 198 of the sequence set forth in SEQ ID NO: 342.
- the epitope comprises a sequence that is identical or corresponds to residues 195, 197, and/or 198 of a sequence that is within the sequence set forth in SEQ ID NO: 342.
- the epitope has a sequence that has a 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% identity to a sequence that is within the sequence set forth in SEQ ID NO: 342. In some aspects, the epitope has 1, 2, 3, 4, 5, 6, 7, 8, or 9 substitutions from a sequence that is within the sequence set forth in forth in SEQ ID NO: 342. In some aspects, the epitope has 1, 2, or 3 substitutions from residues a sequence that is within the sequence set forth in SEQ ID NO: 342. In some aspects, the antibody makes contact with any of the residues set forth in FIG. 9 .
- the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 76. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 77. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 78. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 79.
- the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 80. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 81. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 82. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 83. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 84.
- the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 85. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 86. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 87. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 88. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 89.
- the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 90. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 91. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 92. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 93. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 94.
- the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 95. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 96. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 97. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 98. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 99.
- the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 100. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 101.
- the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-H3 sequence provided in this disclosure. In some aspects, the CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-H3 sequences provided in this disclosure. In some aspects, the CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a V H sequence comprising one or more CDR-H sequences comprising, consisting of, or consisting essentially of one or more illustrative CDR-H sequences provided in this disclosure, and variants thereof.
- the antibody comprises a V H sequence comprising one or more Kabat CDR-H sequences comprising, consisting of, or consisting essentially of one or more illustrative Kabat CDR-H sequences provided in this disclosure, and variants thereof.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 76. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 77. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 78.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 79. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 80. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 81. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 82.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 83. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 84. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 85. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 86.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 87. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 88. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 89. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 90.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 91. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 92. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 94. In some aspects, the antibody comprises a VF sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 95.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising consisting of, or consisting essentially of SEQ ID NO: 96. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 97. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 98. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 99.
- the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 54-71. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 54. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 55. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 56.
- the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 57. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 58. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 59. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 60.
- the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 61. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 62. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 63. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 64.
- the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 65. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 66. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 67. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 68.
- the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 69. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 70. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 71.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 18-34. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 18. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 19. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 20.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 21. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 22. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 23. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 24.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 25. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 26. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 27. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 28.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 29. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 30. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 31. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 32.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 33. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 34.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101, and a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 54-71.
- the Kabat CDR-H3 sequence and the Kabat CDR-H2 sequence are both from a single illustrative V H sequence provided in this disclosure.
- the Kabat CDR-H3 and Kabat CDR-H2 are both from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101, and a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 18-34.
- the Kabat CDR-H3 sequence and the Kabat CDR-H1 sequence are both from a single illustrative V H sequence provided in this disclosure.
- the Kabat CDR-H3 and Kabat CDR-H1 are both from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 18-34 and a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 54-71.
- the Kabat CDR-H1 sequence and the Kabat CDR-H2 sequence are both from a single illustrative V H sequence provided in this disclosure.
- the Kabat CDR-H1 and Kabat CDR-H2 are both from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 18-34, a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 54-71, and a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101.
- the Kabat CDR-H1 sequence, Kabat CDR-H2 sequence, and Kabat CDR-H3 sequence are all from a single illustrative V H sequence provided in this disclosure.
- the Kabat CDR-H1, Kabat CDR-H2, and Kabat CDR-H3 are all from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 18, a Kabat CDR-H2 sequence comprising SEQ ID NO: 54, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 19, a Kabat CDR-H2 sequence comprising SEQ ID NO: 55, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 77.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 20, a Kabat CDR-H2 sequence comprising SEQ ID NO: 56, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 78. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 79.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 22, a Kabat CDR-H2 sequence comprising SEQ ID NO: 58, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 80.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 60, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 81.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 82. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 81.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 83.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 84.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 24, a Kabat CDR-H2 sequence comprising SEQ ID NO: 61, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 85.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 24, a Kabat CDR-H2 sequence comprising SEQ ID NO: 61, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 86. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 25, a Kabat CDR-H2 sequence comprising SEQ ID NO: 62, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 63, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 88. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 63, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 89.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 25, a Kabat CDR-H2 sequence comprising SEQ ID NO: 63, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 90.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 27, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 90.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 28, a Kabat CDR-H2 sequence comprising SEQ ID NO: 62, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 91. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 29, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 92.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 25, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 93. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 66, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 94.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 31, a Kabat CDR-H2 sequence comprising SEQ ID NO: 67, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 95.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 32, a Kabat CDR-H2 sequence comprising SEQ ID NO: 68, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 96.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 97. In some aspects, the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 34, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 98.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 18, a Kabat CDR-H2 sequence comprising SEQ ID NO: 54, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 99.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 31, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 100.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 24, a Kabat CDR-H2 sequence comprising SEQ ID NO: 61, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 101.
- the V H sequences provided herein comprise a variant of an illustrative Kabat CDR-H3, CDR-H2, and/or CDR-H1 sequence provided in this disclosure.
- the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H3 sequence provided in this disclosure. In some aspects, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Kabat CDR-H3 sequences provided in this disclosure. In some aspects, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H2 sequence provided in this disclosure. In some aspects, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Kabat CDR-H2 sequences provided in this disclosure. In some aspects, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H1 sequence provided in this disclosure. In some aspects, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Kabat CDR-H1 sequences provided in this disclosure. In some aspects, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a V H sequence comprising one or more Chothia CDR-H sequences comprising, consisting of, or consisting essentially of one or more illustrative Chothia CDR-H sequences provided in this disclosure, and variants thereof.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 76. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 77.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 78. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 79. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 80. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 81.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 82. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 83. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 84. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 85.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 86. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 87. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 88. In some aspects, the antibody comprises a Vii sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 89.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 90. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 91. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 92. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 93.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 94. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 95. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 96. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 97.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 98. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 99. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 100. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 101.
- the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 38-50. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 38. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 39. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 40.
- the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 41. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 42. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 43. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 44.
- the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 45. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 46. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 47. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 48.
- the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 49. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 50.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-14. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 1. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 2. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 3.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 4. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 5. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 6. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 7.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 8. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 9. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 10. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 11.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 12. In some aspects, the antibody comprises a VF sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 13. In some aspects, the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 14.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101, and a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 38-50.
- the Chothia CDR-H3 sequence and the Chothia CDR-H2 sequence are both from a single illustrative V H sequence provided in this disclosure.
- the Chothia CDR-H3 and Chothia CDR-H2 are both from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101, and a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-14.
- the Chothia CDR-H3 sequence and the Chothia CDR-H1 sequence are both from a single illustrative V H sequence provided in this disclosure.
- the Chothia CDR-H3 and Chothia CDR-H1 are both from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-14 and a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 38-50.
- the Chothia CDR-H1 sequence and the Chothia CDR-H2 sequence are both from a single illustrative V H sequence provided in this disclosure.
- the Chothia CDR-H1 and Chothia CDR-H2 are both from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-14, a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 38-50, and a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 76-101.
- the Chothia CDR-H1 sequence, Chothia CDR-H2 sequence, and Chothia CDR-H3 sequence are all from a single illustrative V H sequence provided in this disclosure.
- the Chothia CDR-H1, Chothia CDR-H2, and Chothia CDR-H3 are all from a single illustrative V H sequence selected from SEQ ID NOS: 170-200.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H2 sequence comprising SEQ ID NO: 38, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 39, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 77.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 40, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 78.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 79.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 4, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 80.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 43, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 81.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 82.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 5, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 81.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 83.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 84.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 85.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 86.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 7, a Chothia CDR-H2 sequence comprising SEQ ID NO: 45, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 8, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 88.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 8, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 89.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 7, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 90.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 9, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 90.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 45, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 91.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 8, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 92.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 7, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 93.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 46, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 94.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 11, a Chothia CDR-H2 sequence comprising SEQ ID NO: 47, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 95.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 12, a Chothia CDR-H2 sequence comprising SEQ ID NO: 48, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 96.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 13, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 97.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 14, a Chothia CDR-H2 sequence comprising SEQ ID NO: 49, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 98.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H2 sequence comprising SEQ ID NO: 38, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 99.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 11, a Chothia CDR-H2 sequence comprising SEQ ID NO: 50, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 100.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 101.
- the V H sequences provided herein comprise a variant of an illustrative Chothia CDR-H3, CDR-H2, and/or CDR-H1 sequence provided in this disclosure.
- the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H3 sequence provided in this disclosure. In some aspects, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Chothia CDR-H3 sequences provided in this disclosure. In some aspects, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H2 sequence provided in this disclosure. In some aspects, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Chothia CDR-H2 sequences provided in this disclosure. In some aspects, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H1 sequence provided in this disclosure. In some aspects, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Chothia CDR-H1 sequences provided in this disclosure. In some aspects, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 170-200. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 170. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 171. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 172. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 173.
- the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 174. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 175. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 176. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 177. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 178.
- the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 179. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 180. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 181. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 182. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 183.
- the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 184. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 185. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 186. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 187. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 188.
- the antibody comprises a V H sequence comprising, consisting of or consisting essentially of SEQ ID NO: 189. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 190. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 191. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 192. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 193.
- the antibody comprises a V H sequence comprising, consisting of or consisting essentially of SEQ ID NO: 194. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 195. In some aspects, the antibody comprises a Vii sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 196. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 197. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 198.
- the antibody comprises a V H sequence comprising, consisting of or consisting essentially of SEQ ID NO: 199. In some aspects, the antibody comprises a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 200.
- V H sequences provided herein comprise, consist of, or consist essentially of a variant of an illustrative V H sequence provided in this disclosure.
- the V H sequence comprises, consists of, or consists essentially of a variant of an illustrative V H sequence provided in this disclosure. In some aspects, the V H sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identity with any of the illustrative V H sequences provided in this disclosure.
- the V H sequence comprises, consists of, or consists essentially of any of the illustrative V H sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions.
- the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 149-166. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 149. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 150. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 151. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 152.
- the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 153. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 154. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 155. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 156. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 157.
- the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 158. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 159. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 160. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 161. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 162.
- the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 163. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 164. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 165. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 166.
- the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a V L sequence comprising one or more CDR-L sequences comprising, consisting of, or consisting essentially of one or more illustrative CDR-L sequences provided in this disclosure, and variants thereof.
- the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 149-166. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 149. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 150. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 151.
- the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 152. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 153. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 154. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 155.
- the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 156. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 157. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 158. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 159.
- the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 160. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 161. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 162. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 163.
- the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 164. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 165. In some aspects, the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 166.
- the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 128-145. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 128. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 129. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 130.
- the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 131. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 132. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 133. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 134.
- the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 135. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 136. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 137. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 138.
- the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 139. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 140. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 141. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 142.
- the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 143. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 144. In some aspects, the antibody comprises a V L sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 145.
- the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 105-124. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 105. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 106. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 107.
- the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 108. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 109. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 110. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 111.
- the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 112. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 113. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 114. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 115.
- the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 116. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 117. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 18. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 119.
- the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 120. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 121. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 122. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 123. In some aspects, the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 124.
- the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 149-166 and a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 128-145.
- the CDR-L3 sequence and the CDR-L2 sequence are both from a single illustrative V L sequence provided in this disclosure.
- the CDR-L3 and CDR-L2 are both from a single illustrative V L sequence selected from SEQ ID NOS: 204-228.
- the antibody comprises a V L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 149-166 and a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 105-124.
- the CDR-L3 sequence and the CDR-L1 sequence are both from a single illustrative V L sequence provided in this disclosure.
- the CDR-L3 and CDR-L1 are both from a single illustrative V L sequence selected from SEQ ID NOS: 204-228.
- the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 105-124 and a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 128-145.
- the CDR-L1 sequence and the CDR-L2 sequence are both from a single illustrative V L sequence provided in this disclosure.
- the CDR-L1 and CDR-L2 are both from a single illustrative V L sequence selected from SEQ ID NOS: 204-228.
- the antibody comprises a V L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 105-124, a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 128-145, and a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 149-166.
- the CDR-L1 sequence, CDR-L2 sequence, and CDR-L3 sequence are all from a single illustrative V L sequence provided in this disclosure.
- the CDR-L1, CDR-L2, and CDR-L3 are all from a single illustrative V L sequence selected from SEQ ID NOS: 204-228.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 106, a CDR-L2 sequence comprising SEQ ID NO: 129, and a CDR-L3 sequence SEQ ID NO: 150.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 107, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 151. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 108, a CDR-L2 sequence comprising SEQ ID NO: 130, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 109, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence SEQ ID NO: 152. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 107, a CDR-L2 sequence comprising SEQ ID NO: 132, and a CDR-L3 sequence SEQ ID NO: 153.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 132, and a CDR-L3 sequence SEQ ID NO: 151. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 111, a CDR-L2 sequence comprising SEQ ID NO: 133, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 154. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 112, a CDR-L2 sequence comprising SEQ ID NO: 134, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 113, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence SEQ ID NO: 156. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 114, a CDR-L2 sequence comprising SEQ ID NO: 136, and a CDR-L3 sequence SEQ ID NO: 157.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence SEQ ID NO: 157. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 116, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 117, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence SEQ ID NO: 155. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence SEQ ID NO: 158.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence SEQ ID NO: 155. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 119, a CDR-L2 sequence comprising SEQ ID NO: 139, and a CDR-L3 sequence SEQ ID NO: 159.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 120, a CDR-L2 sequence comprising SEQ ID NO: 140, and a CDR-L3 sequence SEQ ID NO: 160. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 141, and a CDR-L3 sequence SEQ ID NO: 161.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 122, a CDR-L2 sequence comprising SEQ ID NO: 142, and a CDR-L3 sequence SEQ ID NO: 162.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 143, and a CDR-L3 sequence SEQ ID NO: 163.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 143, and a CDR-L3 sequence SEQ ID NO: 164. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 123, a CDR-L2 sequence comprising SEQ ID NO: 144, and a CDR-L3 sequence SEQ ID NO: 165.
- the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 124, a CDR-L2 sequence comprising SEQ ID NO: 145, and a CDR-L3 sequence SEQ ID NO: 166.
- the V L sequences provided herein comprise a variant of an illustrative CDR-L3, CDR-L2, and/or CDR-L1 sequence provided in this disclosure.
- the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the CDR-L2 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L2 sequence provided in this disclosure. In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L2 sequences provided in this disclosure. In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the CDR-L1 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L1 sequence provided in this disclosure. In some aspects, the CDR-L sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L sequences provided in this disclosure. In some aspects, the CDR-L1 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 204-228. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 204. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 205. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 206. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 207.
- the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 208. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 209. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 210. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 211. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 212.
- the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 213. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 214. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 215. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 216. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 217.
- the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 218. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 219. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 220. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 221. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 222.
- the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 223. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 224. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 225. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 226. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 227. In some aspects, the antibody comprises a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 228.
- V L sequences provided herein comprise, consist of, or consist essentially of a variant of an illustrative V L sequence provided in this disclosure.
- the V L sequence comprises, consists of, or consists essentially of a variant of an illustrative V L sequence provided in this disclosure. In some aspects, the V L sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.05% identity with any of the illustrative V L sequences provided in this disclosure.
- the V L sequence comprises, consists of, or consists essentially of any of the illustrative V L sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions.
- the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a CDR-H3 sequence and a CDR-L3 sequence.
- the CDR-H3 sequence is part of a V H and the CDR-L3 sequence is part of a V L .
- the CDR-H3 sequence is a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 76-101
- the CDR-L3 sequence is a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 149-166.
- the CDR-H3 sequence is SEQ ID NO: 76 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 77 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 78 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 79 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 80 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 81 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 82 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 83 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 84 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 85 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 86 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 87 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 88 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 89 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 90 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 91 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 92 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 93 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 94 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 95 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 96 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 97 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 98 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 99 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166.
- the CDR-L3 sequence is SEQ ID NO: 149.
- the CDR-L3 sequence is SEQ ID NO: 150.
- the CDR-L3 sequence is SEQ ID NO: 151.
- the CDR-L3 sequence is SEQ ID NO: 152.
- the CDR-L3 sequence is SEQ ID NO: 153.
- the CDR-L3 sequence is SEQ ID NO: 154.
- the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 100 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3 sequence is SEQ ID NO: 101 and the CDR-L3 sequence is selected from SEQ ID NOS: 149-166. In some aspects, the CDR-L3 sequence is SEQ ID NO: 149. In some aspects, the CDR-L3 sequence is SEQ ID NO: 150. In some aspects, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155.
- the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some aspects, the CDR-L3 sequence is SEQ ID NO: 165. In some aspects, the CDR-L3 sequence is SEQ ID NO: 166.
- the CDR-H3-CDR-L3 pairs provided herein comprise a variant of an illustrative CDR-H3 and/or CDR-L1 sequence provided in this disclosure.
- the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-H3 sequence provided in this disclosure. In some aspects, the CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-H3 sequences provided in this disclosure. In some aspects, the CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises a V H sequence and a V L sequence.
- the V H sequence is a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 170-200 and the V L sequence is a V L sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 204-228.
- the V H sequence is SEQ ID NO: 170 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V H sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 171 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 172 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V H sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 173 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 174 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 175 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 176 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 177 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 178 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 179 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 180 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 181 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 182 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V H sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 183 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the VF sequence is SEQ ID NO: 184 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 185 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 186 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 187 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 188 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 189 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V H sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 190 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 191 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 192 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the VF sequence is SEQ ID NO: 193 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 194 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 195 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L , sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213.
- the V H sequence is SEQ ID NO: 214.
- the V L sequence is SEQ ID NO: 215.
- the V L sequence is SEQ ID NO: 216.
- the V L sequence is SEQ ID NO: 217.
- the V L sequence is SEQ ID NO: 218.
- the V L sequence is SEQ ID NO: 219.
- the V L sequence is SEQ ID NO: 220.
- the V L sequence is SEQ ID NO: 221.
- the V L sequence is SEQ ID NO: 222.
- the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 196 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 197 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V L sequence is SEQ ID NO: 198 and the V L sequence is selected from SEQ ID NOS: 204-228. In some aspects, the V L sequence is SEQ ID NO: 204. In some aspects, the V L sequence is SEQ ID NO: 205. In some aspects, the V L sequence is SEQ ID NO: 206. In some aspects, the V L sequence is SEQ ID NO: 207. In some aspects, the V L sequence is SEQ ID NO: 208. In some aspects, the V L sequence is SEQ ID NO: 209. In some aspects, the V L sequence is SEQ ID NO: 210. In some aspects, the V L sequence is SEQ ID NO: 211. In some aspects, the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 199 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V L sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the V H sequence is SEQ ID NO: 200 and the V L sequence is selected from SEQ ID NOS: 204-228.
- the V L sequence is SEQ ID NO: 204.
- the V L sequence is SEQ ID NO: 205.
- the V L sequence is SEQ ID NO: 206.
- the V L sequence is SEQ ID NO: 207.
- the V L sequence is SEQ ID NO: 208.
- the V L sequence is SEQ ID NO: 209.
- the V L sequence is SEQ ID NO: 210.
- the V L sequence is SEQ ID NO: 211.
- the V L sequence is SEQ ID NO: 212.
- the V L sequence is SEQ ID NO: 213. In some aspects, the V L sequence is SEQ ID NO: 214. In some aspects, the V L sequence is SEQ ID NO: 215. In some aspects, the V L sequence is SEQ ID NO: 216. In some aspects, the V L sequence is SEQ ID NO: 217. In some aspects, the V L sequence is SEQ ID NO: 218. In some aspects, the V L sequence is SEQ ID NO: 219. In some aspects, the V L sequence is SEQ ID NO: 220. In some aspects, the V L sequence is SEQ ID NO: 221. In some aspects, the V L sequence is SEQ ID NO: 222. In some aspects, the V L sequence is SEQ ID NO: 223.
- the V H sequence is SEQ ID NO: 224. In some aspects, the V L sequence is SEQ ID NO: 225. In some aspects, the V L sequence is SEQ ID NO: 226. In some aspects, the V L sequence is SEQ ID NO: 227. In some aspects, the V L sequence is SEQ ID NO: 228.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 18, a Kabat CDR-H2 sequence comprising SEQ ID NO: 54, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76 and a V L sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 19, a Kabat CDR-H2 sequence comprising SEQ ID NO: 55, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 77 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 20, a Kabat CDR-H2 sequence comprising SEQ ID NO: 56, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 78 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 79 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 22, a Kabat CDR-H2 sequence comprising SEQ ID NO: 58, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 80 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 106, a CDR-L2 sequence comprising SEQ ID NO: 129, and a CDR-L3 sequence SEQ ID NO: 150.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 107, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 60, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 81 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 108, a CDR-L2 sequence comprising SEQ ID NO: 130, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 82 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 109, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence SEQ ID NO: 152.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 76 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 107, a CDR-L2 sequence comprising SEQ ID NO: 132, and a CDR-L3 sequence SEQ ID NO:153.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 23, a Kabat CDR-H2 sequence comprising SEQ ID NO: 59, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 81 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 132, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 83 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 111, a CDR-L2 sequence comprising SEQ ID NO: 133, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 21, a Kabat CDR-H2 sequence comprising SEQ ID NO: 57, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 84 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 24, a Kabat CDR-H2 sequence comprising SEQ ID NO: 61, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 85 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 154.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 24, a Kabat CDR-H2 sequence comprising SEQ ID NO: 61, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 86 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 154.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 25, a Kabat CDR-H2 sequence comprising SEQ ID NO: 62, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 112, a CDR-L2 sequence comprising SEQ ID NO: 134, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Kabat CDR-H sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 63, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 88 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 113, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence SEQ ID NO: 156.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 63, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 89 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 114, a CDR-L2 sequence comprising SEQ ID NO: 136, and a CDR-L3 sequence SEQ ID NO: 157.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 25, a Kabat CDR-H2 sequence comprising SEQ ID NO: 63, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 90 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence SEQ ID NO: 157.
- the antibody comprises a V H sequence comprising a Kabat CDR-H sequence comprising SEQ ID NO: 27, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 90 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 116, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 28, a Kabat CDR-H2 sequence comprising SEQ ID NO: 62, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 91 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 117, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 29, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 92 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence SEQ ID NO: 158.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 25, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 93 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 66, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 94 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 119, a CDR-L2 sequence comprising SEQ ID NO: 139, and a CDR-L3 sequence SEQ ID NO: 159.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 31, a Kabat CDR-H2 sequence comprising SEQ ID NO: 67, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 95 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 120, a CDR-L2 sequence comprising SEQ ID NO: 140, and a CDR-L3 sequence SEQ ID NO: 160.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 32, a Kabat CDR-H2 sequence comprising SEQ ID NO: 68, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 96 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 141, and a CDR-L3 sequence SEQ ID NO: 161.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 97 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 122, a CDR-L2 sequence comprising SEQ ID NO: 142, and a CDR-L3 sequence SEQ ID NO: 162.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 34, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 98 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 143, and a CDR-L3 sequence SEQ ID NO: 163.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 18, a Kabat CDR-H2 sequence comprising SEQ ID NO: 54, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 99 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 143, and a CDR-L3 sequence SEQ ID NO: 164.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 31, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 100 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 123, a CDR-L2 sequence comprising SEQ ID NO: 144, and a CDR-L3 sequence SEQ ID NO: 165.
- the antibody comprises a V H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 24, a Kabat CDR-H2 sequence comprising SEQ ID NO: 61, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 101 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 124, a CDR-L2 sequence comprising SEQ ID NO: 145, and a CDR-L3 sequence SEQ ID NO: 166.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H2 sequence comprising SEQ ID NO: 38, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 39, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 77 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 40, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 78 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 79 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 4, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 80 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 106, a CDR-L2 sequence comprising SEQ ID NO: 129, and a CDR-L3 sequence SEQ ID NO: 150.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 107, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 43, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 81 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 108, a CDR-L2 sequence comprising SEQ ID NO: 130, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 82 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 109, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence SEQ ID NO: 152.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 5, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 76 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 107, a CDR-L2 sequence comprising SEQ ID NO: 132, and a CDR-L3 sequence SEQ ID NO: 153.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 2, a Chothia CDR-H2 sequence comprising SEQ ID NO: 42, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 81 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 132, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 83 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 111, a CDR-L2 sequence comprising SEQ ID NO: 133, and a CDR-L3 sequence SEQ ID NO: 151.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 3, a Chothia CDR-H2 sequence comprising SEQ ID NO: 41, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 84 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 149.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 85 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 154.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 86 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 154.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 7, a Chothia CDR-H2 sequence comprising SEQ ID NO: 45, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 112, a CDR-L2 sequence comprising SEQ ID NO: 134, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 8, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 88 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 113, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence SEQ ID NO: 156.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 8, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 89 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 114, a CDR-L2 sequence comprising SEQ ID NO: 136, and a CDR-L3 sequence SEQ ID NO: 157.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 7, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 90 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence SEQ ID NO: 157.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 9, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 90 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 116, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 45, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 91 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 117, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 8, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 92 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence SEQ ID NO: 158.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 7, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 93 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence SEQ ID NO: 155.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 46, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 94 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 119, a CDR-L2 sequence comprising SEQ ID NO: 139, and a CDR-L3 sequence SEQ ID NO: 159.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 11, a Chothia CDR-H2 sequence comprising SEQ ID NO: 47, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 95 and a VL sequence comprising a CDR-L sequence comprising SEQ ID NO: 120, a CDR-L2 sequence comprising SEQ ID NO: 140, and a CDR-L3 sequence SEQ ID NO: 160.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 12, a Chothia CDR-H2 sequence comprising SEQ ID NO: 48, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 96 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 141, and a CDR-L3 sequence SEQ ID NO: 161.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 13, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 97 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 122, a CDR-L2 sequence comprising SEQ ID NO: 142, and a CDR-L3 sequence SEQ ID NO: 162.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 14, a Chothia CDR-H2 sequence comprising SEQ ID NO: 49, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 98 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 143, and a CDR-L3 sequence SEQ ID NO: 163.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H2 sequence comprising SEQ ID NO: 38, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 99 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 105, a CDR-L2 sequence comprising SEQ ID NO: 143, and a CDR-L3 sequence SEQ ID NO: 164.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 11, a Chothia CDR-H2 sequence comprising SEQ ID NO: 50, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 100 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 123, a CDR-L2 sequence comprising SEQ ID NO: 144, and a CDR-L3 sequence SEQ ID NO: 165.
- the antibody comprises a V H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 6, a Chothia CDR-H2 sequence comprising SEQ ID NO: 44, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 101 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 124, a CDR-L2 sequence comprising SEQ ID NO: 145, and a CDR-L3 sequence SEQ ID NO: 166.
- V H -V L pairs provided herein comprise a variant of an illustrative V H and/or V L sequence provided in this disclosure.
- the V H sequence comprises, consists of, or consists essentially of a variant of an illustrative V H sequence provided in this disclosure. In some aspects, the V H sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.1% identity with any of the illustrative V H sequences provided in this disclosure.
- the V H sequence comprises, consists of, or consists essentially of any of the illustrative V H sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions.
- the amino acid substitutions are conservative amino acid substitutions.
- the V L sequence comprises, consists of, or consists essentially of a variant of an illustrative V L sequence provided in this disclosure. In some aspects, the V L sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.05% identity with any of the illustrative V L sequences provided in this disclosure.
- the V L sequence comprises, consists of, or consists essentially of any of the illustrative V L sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions.
- the amino acid substitutions are conservative amino acid substitutions.
- the antibody comprises or consists of one or more heavy chains consisting of an HC sequence and one or more light chains consisting of an LC sequence. In some aspects, the antibody comprises or consists of two identical heavy chains consisting of an HC sequence and two identical light chains consisting of an LC sequence.
- the HC sequence is an HC sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 232-262 and the LC sequence is an LC sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 300-330.
- the HC sequence is an HC sequence consisting of a sequence selected from SEQ ID NOS: 232-262 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the HC sequence is an HC sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 266-296 and the LC sequence is an LC sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 300-330.
- the HC sequence is an HC sequence consisting of a sequence selected from SEQ ID NOS: 266-296 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 232 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 233 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 234 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 235 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 236 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 237 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 238 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 239 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 240 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 241 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 242 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 243 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 244 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 245 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 246 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 247 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 248 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 249 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 250 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 251 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 252 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 253 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 254 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 255 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 256 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 257 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 258 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 259 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 260 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 261 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 262 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 266 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 267 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 268 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 269 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 270 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 271 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 272 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 273 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 274 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 275 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 276 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 277 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 278 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 279 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 280 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 281 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 282 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 283 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 284 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 285 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 286 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 287 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 288 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 289 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 290 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 291 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 292 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 293 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 294 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 295 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 296 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 300-330.
- the LC sequence is SEQ ID NO: 300.
- the LC sequence is SEQ ID NO: 301.
- the LC sequence is SEQ ID NO: 302.
- the LC sequence is SEQ ID NO: 303.
- the LC sequence is SEQ ID NO: 304.
- the LC sequence is SEQ ID NO: 305.
- the LC sequence is SEQ ID NO: 306.
- the LC sequence is SEQ ID NO: 307.
- the LC sequence is SEQ ID NO: 308. In some aspects, the LC sequence is SEQ ID NO: 309. In some aspects, the LC sequence is SEQ ID NO: 310. In some aspects, the LC sequence is SEQ ID NO: 311. In some aspects, the LC sequence is SEQ ID NO: 312. In some aspects, the LC sequence is SEQ ID NO: 313. In some aspects, the LC sequence is SEQ ID NO: 314. In some aspects, the LC sequence is SEQ ID NO: 315. In some aspects, the LC sequence is SEQ ID NO: 316. In some aspects, the LC sequence is SEQ ID NO: 317. In some aspects, the LC sequence is SEQ ID NO: 318.
- the LC sequence is SEQ ID NO: 319. In some aspects, the LC sequence is SEQ ID NO: 320. In some aspects, the LC sequence is SEQ ID NO: 321. In some aspects, the LC sequence is SEQ ID NO: 322. In some aspects, the LC sequence is SEQ ID NO: 323. In some aspects, the LC sequence is SEQ ID NO: 324. In some aspects, the LC sequence is SEQ ID NO: 325. In some aspects, the LC sequence is SEQ ID NO: 326. In some aspects, the LC sequence is SEQ ID NO: 327. In some aspects, the LC sequence is SEQ ID NO: 328. In some aspects, the LC sequence is SEQ ID NO: 329. In some aspects, the LC sequence is SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 232 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 300. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 233 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 301. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 234 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 302. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 235 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 303.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 236 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 304. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 237 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 305. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 238 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 306. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 239 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 307.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 240 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 308.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 241 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 309.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 242 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 310.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 243 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 311.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 244 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 312. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 245 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 313. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 246 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 314. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 247 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 315.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 248 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 316. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 249 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 317. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 250 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 318. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 251 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 319.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 252 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 320. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 253 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 321. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 254 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 322. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 255 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 323.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 256 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 324. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 257 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 325. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 258 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 326. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 259 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 327.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 260 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 328. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 261 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 329. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 262 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 330.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 266 and the LC sequence is an LC sequence consisting of a sequence SEQ ID NO: 300. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 267 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 301. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 268 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 302. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 269 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 303.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 270 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 304. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 271 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 305. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 272 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 306. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 273 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 307.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 274 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 308. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 275 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 309. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 276 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 310. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 277 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 311.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 278 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 312. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 279 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 313. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 280 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 314. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 281 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 315.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 282 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 316. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 283 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 317. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 284 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 318. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 285 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 319.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 286 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 320. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 287 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 321. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 288 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 322. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 289 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 323.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 290 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 324. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 291 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 325. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 292 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 326. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 293 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 327.
- the HC sequence is an HC sequence consisting of SEQ ID NO: 294 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 328. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 295 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 329. In some aspects, the HC sequence is an HC sequence consisting of SEQ ID NO: 296 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 330.
- anti-HLA-G antibodies comprising one or more sequences defined by consensus sequences.
- Each consensus sequence is based, at least in part, on one or more alignments of two or more useful anti-HLA-G CDR sequences provided in this disclosure. Based on such alignments, a person of skill in the art would recognize that different amino acid residues may useful in certain positions of the CDRs. Accordingly, each consensus sequence encompasses two or more useful anti-HLA-G CDR sequences.
- the antibody comprises a CDR-H3 sequence defined by the consensus sequence G-y 2 -y 3 -R-A-V-P-F-y 9 -y 10 (SEQ ID NOS: 76-84), where y 2 is I, P, Q, T, or V; y 3 is A, F, K, or R; y 9 is A, D, Q, or V; y 10 is D, R, or Y.
- y 2 when y 2 is I; y 3 is A or R; y 9 is F; and y 10 is Y.
- y 2 when y 2 is V; y 3 is R; y 9 is A, D, Q, or V; and y 10 is D, R, or Y.
- y 3 when y 3 is R; y 2 is 1, T, or V; y 9 is A, D, or Q; and y 10 is D, R, or Y.
- y 10 when y 10 is Y; y 2 is I, P, R, or V; y 3 is A, F, K, or R; and y 9 is D. In some aspects, when Yon is D; y 2 is V; y 3 is R; and y 9 is A or V.
- y 2 when y 2 is V; y 3 is R: y 9 is D; and y 10 is Y.
- y 2 when y 2 is I; y 3 is A; Y is D; and y 10 is Y.
- y 2 when y 2 is V; y 3 is R; Y is Q; and y 10 is R.
- y 2 when y 2 is T; y 3 is R; y 9 is D; and y 10 is Y.
- y 2 when y 2 is V; y 3 is R; y 9 is A; and y 10 is D. In some aspects, when y 2 is I; y 3 is R; y 9 is D; and y 10 is Y. In some aspects, when y 2 is Q; y 3 is F; y 9 is D; and y 10 is Y.
- the antibody comprises a CDR-H3 sequence defined by the consensus sequence G-G- ⁇ 3 - ⁇ 4 - ⁇ 5 -Y-S-R-G-P- ⁇ 11 -D-V (SEQ ID NOS: 85-93), where ⁇ 3 is E, G, Q, or T; ⁇ 4 is A, H, P, Q. or V; ⁇ 5 is K or T; and ⁇ 11 is F, L, or M.
- ⁇ 3 is G; when ⁇ 4 is A or Q; ⁇ 5 is T; and ⁇ 11 is V.
- ⁇ 3 is T; when ⁇ 4 is H, P, or V; ⁇ 5 is I, T, or Y; and ⁇ 11 is V.
- ⁇ 4 is H; when ⁇ 3 is T; ⁇ 5 is T; and ⁇ 11 is F, L, or M.
- ⁇ 4 is V; when ⁇ 3 is E, T, or Q; ⁇ 5 is K or T; and ⁇ 11 is L.
- ⁇ 5 is T; when ⁇ 3 is E, G.
- ⁇ 4 is A, H, Q, or V; and ⁇ 11 is F, L, or M.
- ⁇ 11 is L; when ⁇ 3 is E, G, T, or Q; ⁇ 4 is A, H, P, Q, or V; and ⁇ 5 is I, K, or T.
- the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence Y- ⁇ 2 -S- ⁇ 4 -S(SEQ ID NOS: 38 and 44-45), where ⁇ 2 is H or Y and ⁇ 4 is A or G.
- ⁇ 2 when ⁇ 2 is H; ⁇ 4 is A or G. In some aspects, when ⁇ 4 is G, ⁇ 2 is H or Y.
- ⁇ 2 when ⁇ 2 is Y; ⁇ 4 is G. In some aspects, when ⁇ 2 is H; ⁇ 4 is G. In some aspects, when ⁇ 2 is H; ⁇ 4 is A.
- the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ⁇ 1 - ⁇ 2 -S-G-S(SEQ ID NOS: 39, 41-42, and 49), where ⁇ 1 is A, H, or S; and ⁇ 2 is S or Y.
- ⁇ 1 is S; ⁇ 2 is S or Y.
- ⁇ 1 when ⁇ 1 is S; ⁇ 2 is S. In some aspects, when ⁇ 1 is S; ⁇ 2 is Y. In some aspects, when ⁇ 1 is H; ⁇ 2 is Y. In some aspects, when ⁇ 1 is A; ⁇ 2 is Y.
- the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ⁇ 1 - ⁇ 2 -S-G- ⁇ 5 - ⁇ 6 (SEQ ID NOS: 56-60), where ⁇ 1 is A or S; ⁇ 2 is G or S; ⁇ 5 is 1 or S; and ⁇ 6 is T or V.
- ⁇ 1 when ⁇ 1 is S, ⁇ 2 is G or S; ⁇ 5 is I or S; and ⁇ 6 is T or V.
- ⁇ 2 when ⁇ 1 is A or S; ⁇ 5 is S; and ⁇ 6 is T or V.
- ⁇ 5 when ⁇ 1 is S, ⁇ 1 is A or S; ⁇ 2 is S; and ⁇ 6 is T or V.
- ⁇ 6 when ⁇ 6 is T, ⁇ 1 is S; ⁇ 2 is G or S; and ⁇ 5 is I or T.
- ⁇ 1 is A; ⁇ 2 is S; ⁇ 5 is S; and ⁇ 6 is V. In some aspects, when ⁇ 1 is S; ⁇ 2 is G; ⁇ 5 is I; and ⁇ 6 is T. In some aspects, when ⁇ 1 is S; ⁇ 2 is S; ⁇ 5 is S; and ⁇ 6 is T.
- the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-G-S-I-S-S- ⁇ 7 - ⁇ 8 - ⁇ 9 (SEQ ID NOS: 1-4 and 13-14), where ⁇ 7 is S or A; Us is D, S, or N; and ⁇ 9 is T, N, Y, or is absent.
- ⁇ 7 is S
- ⁇ 8 is D, N. or S
- ⁇ 9 is T. Y, or is absent.
- ⁇ 8 is D
- ⁇ 7 is S or A
- ⁇ 9 is N, T, or Y.
- ⁇ 8 when ⁇ 8 is T; ⁇ 7 is S; and ⁇ 8 is D or S. In some aspects, when ⁇ 9 is Y; ⁇ 7 is S; and ⁇ 8 is D or S.
- the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-Y-S-I- ⁇ 5 -S-G- ⁇ 8 (SEQ ID NOS: 6-9), where ⁇ 5 is S or L and ⁇ 8 is F, H, or Y.
- ⁇ 5 when ⁇ 5 is S, ⁇ 5 is F, H, or Y.
- ⁇ 5 when ⁇ 5 is S, ⁇ 8 is F. In some aspects, when ⁇ 5 is S, ⁇ 8 is H. In some aspects, when ⁇ 5 is S. ⁇ 8 is Y. In some aspects, when ⁇ 5 is L. ⁇ 8 is Y.
- the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-F-T-F- ⁇ 5 - ⁇ 6 - ⁇ 7 (SEQ ID NOS: 10-12), where ⁇ 5 is D or s; ⁇ 6 is D, N, or S; and ⁇ 7 is S or Y.
- ⁇ 5 when ⁇ 5 is S; ⁇ 6 is D or S; and ⁇ 7 is S or Y. In some aspects, when ⁇ 7 is Y; ⁇ 5 is D or S; and ⁇ 6 is N or D.
- ⁇ 5 when ⁇ 5 is D; ⁇ 6 is N; and ⁇ 7 is Y. In some aspects, when ⁇ 5 is S; ⁇ 6 is D; and ⁇ 7 is Y. In some aspects, when ⁇ 5 is S; ⁇ 6 is S; and ⁇ 7 is S.
- the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence ⁇ 1 -I- ⁇ 3 - ⁇ 4 - ⁇ 5 - ⁇ 6 - ⁇ 7 -T- ⁇ 9 -Y-N-P-S-L-K-S(SEQ ID NOS: 54-65 and 69-70) where ⁇ 1 is A, E, G, or S; ⁇ 3 is A, H, S, or Y; ⁇ 4 , is H, S, or Y; ⁇ 5 is N or S; ⁇ 2 is A or G; ⁇ 7 is A, L, or S; and ⁇ 9 is A, N, L, V, or Y.
- ⁇ 1 is S
- ⁇ 3 is A, H, S, or Y
- ⁇ 4 is H, S, or Y
- ⁇ 5 is N or S
- ⁇ 6 is A or G
- ⁇ 7 is A, L, or S
- ⁇ 9 is A, N, L, V, or Y.
- ⁇ 1 is G
- ⁇ 3 is A or Y
- ⁇ 4 is H or Y
- ⁇ 5 is G or S
- ⁇ 6 is A or G
- ⁇ 7 is S
- ⁇ 9 is A or Y.
- ⁇ 3 when ⁇ 3 is Y; ⁇ 1 is A, E, G, or S; ⁇ 4 is H or Y; ⁇ 5 is S; ⁇ 6 is A or G; ⁇ 7 is S; and ⁇ 9 is A, N, V, or Y.
- ⁇ 3 when ⁇ 3 is S. ⁇ 1 is S; is S or Y; ⁇ 5 is N or S; ⁇ 6 is A or G; ⁇ 7 is L or S; and ⁇ 9 is Y.
- ⁇ 3 when ⁇ 3 is H; ⁇ 1 is S; ⁇ 4 is H or Y; ⁇ 5 is S; ⁇ 6 is G; ⁇ 7 is A or S; and ⁇ 9 is L or Y.
- ⁇ 4 when ⁇ 4 is Y; ⁇ 1 is S or G; ⁇ 3 is A, H, S, or Y; s is N or S; ⁇ 6 is A or G; ⁇ 7 is L or S; and ⁇ 9 is L or Y.
- ⁇ 4 s H when ⁇ 4 s H; ⁇ 1 is A, E, G, S; ⁇ 3 is H or Y; ⁇ 5 is S; ⁇ 6 is A or G; ⁇ 7 is A or S; and ⁇ 9 is A, N, Y or V.
- ⁇ 5 when ⁇ 5 is S; ⁇ 1 is A, E, G, or S; ⁇ 3 is A, H, S, or Y; ⁇ 4 is H, S, or Y; ⁇ 6 is A or G; ⁇ 7 is A or S; and ⁇ 9 is A, L, N, Y, or V.
- ⁇ 6 when ⁇ 6 is G; ⁇ 1 is A, E, G, or S; ⁇ 3 is A, H, S, or Y; ⁇ 4 is H, S, or Y; ⁇ 5 is S; ⁇ 7 is S; and ⁇ 9 is A, N, L, V, or Y.
- ⁇ 6 when ⁇ 6 is A; ⁇ 1 is G or S; ⁇ 3 is S or Y; ⁇ 4 is H or Y; ⁇ 5 is N or S; ⁇ 7 is L or S; and ⁇ 9 is A or Y.
- ⁇ 7 when ⁇ 7 is S; ⁇ 1 is A, E, G, or S; ⁇ 3 is A, H, S, or Y; ⁇ 4 is H, S, or Y; ⁇ 5 is S; ⁇ 6 is A or G; and ⁇ 9 is A, L, N, V, or Y.
- ⁇ 9 when ⁇ 9 is Y; ⁇ 1 is G or S; ⁇ 3 is A, H, S, or Y; ⁇ 4 is H, S or Y; ⁇ 5 is N or S; ⁇ 6 is A or G; and ⁇ 7 is A, L, or S.
- ⁇ 9 when ⁇ 9 is A; ⁇ 1 is G; ⁇ 3 is Y; ⁇ 4 is H; ⁇ 5 is S; ⁇ 6 is A or G; and ⁇ 7 is S.
- ⁇ 1 when ⁇ 1 is G; ⁇ 3 is Y; ⁇ 4 is H; ⁇ 5 is S; ⁇ 6 is G; and ⁇ 7 is S; and ⁇ 9 is Y.
- ⁇ 1 when ⁇ 1 is A; ⁇ 3 is Y; ⁇ 4 is H; ⁇ 5 is S; ⁇ 6 is G; and ⁇ 7 is S; and ⁇ 9 is V.
- ⁇ 1 when ⁇ 1 is G; ⁇ 3 is Y; ⁇ 4 is H; ⁇ 5 is S; ⁇ 6 is G; and ⁇ 7 is S: and ⁇ 9 is A.
- ⁇ 1 is E; ⁇ 3 is Y; ⁇ 4 is H; ⁇ 5 is S; ⁇ 6 is G; and ⁇ 7 is S; and ⁇ 9 is N.
- the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence S-S- ⁇ 3 - ⁇ 4 -Y-W- ⁇ 7 (SEQ ID NOS: 18-21, 23, and 34), where ⁇ 3 is D or S; ⁇ 4 is T or Y; and ⁇ 7 is A, G, or S.
- ⁇ 3 when ⁇ 3 is D; ⁇ 4 is T or Y; and ⁇ 7 is G. In some aspects, when ⁇ 3 is S; ⁇ 4 is T or Y; and ⁇ 7 is A, G, or S. In some aspects, when ⁇ 4 is T; ⁇ 3 is D or S; and ⁇ 7 is A, G, or S. In some aspects, when ⁇ 4 is Y; ⁇ 3 is D or S; and ⁇ 7 is G. In some aspects, when ⁇ 7 is G; ⁇ 3 is D or S; and ⁇ 4 is T or Y.
- the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence S-G- ⁇ 3 -Y-W- ⁇ 6 (SEQ ID NOS: 24-29), where ⁇ 3 is F, H, or Y; and ⁇ 6 is F, G, I, L, or T.
- ⁇ 3 when ⁇ 3 is H, ⁇ 6 is I or T. In some aspects, when ⁇ 3 is Y, ⁇ 6 is F, G, or L. In some aspects, when ⁇ 6 is T, ⁇ 3 is F or H.
- ⁇ 3 when ⁇ 3 is Y, ⁇ 6 is G. In some aspects, when ⁇ 3 is Y, ⁇ 6 is F. In some aspects, when ⁇ 3 is H, ⁇ 6 is I. In some aspects, when ⁇ 3 is F, ⁇ 6 is T. In some aspects, when ⁇ 3 is Y, ⁇ 6 is L. In some aspects, when ⁇ 3 is H, ⁇ 6 is T.
- the antibody comprises a CDR-L3 sequence defined by the consensus sequence Q- ⁇ 2 - ⁇ 3 - ⁇ 4 -H-S-P-Y-T (SEQ ID NOS: 149-153), where ⁇ 2 is Q or W; ⁇ 3 is A, T, or V; and ⁇ 4 is I or V.
- ⁇ 2 when ⁇ 2 is Q; ⁇ 3 is A, T, or V; and ⁇ 4 is I or V. In some aspects, when ⁇ 3 is A; ⁇ 2 is Q or W; and ⁇ 4 is I or V. In some aspects, when ⁇ 4 is V; ⁇ 2 is Q or W; and ⁇ 3 is A, T, or V.
- ⁇ 2 when ⁇ 2 is Q; ⁇ 3 is A; and ⁇ 4 is V. In some aspects, when ⁇ 2 is W; A; is A; and ⁇ 4 is V. In some aspects, when ⁇ 2 is Q; ⁇ 3 is V; and ⁇ 4 is V. In some aspects, when ⁇ 2 is Q; ⁇ 3 is T; and ⁇ 4 is V. In some aspects, when ⁇ 2 is Q; ⁇ 3 is A; and ⁇ 4 is I.
- the antibody comprises a CDR-L3 sequence defined by the consensus sequence Q-Q- ⁇ 3 -S- ⁇ 5 -Y-P-P-T (SEQ ID NOS: 154-158), where ⁇ 3 is F, H, or V; and ⁇ 5 is I, L, or S.
- ⁇ 3 when ⁇ 3 is H; ⁇ 5 is I, L, or S. In some aspects, when ⁇ 5 is H; ⁇ 3 is F, H, or V.
- ⁇ 3 when ⁇ 3 is H, ⁇ 5 is S. In some aspects, when ⁇ 3 is H, ⁇ 5 is L. In some aspects, when ⁇ 3 is F, ⁇ 5 is S. In some aspects, when ⁇ 3 is V, ⁇ 5 is S. In some aspects, when ⁇ 3 is H, ⁇ 5 is I.
- the antibody comprises a CDR-L3 sequence defined by the consensus sequence Q-Q- ⁇ 3 - ⁇ 4 - ⁇ 5 - ⁇ 6 -P-I-T (SEQ ID NOS: 160-161 and 163-164), where ⁇ 3 is A, L, V, or Y; ⁇ 4 is G, P, V, or Y; ⁇ 5 is S, L, or F; and ⁇ 6 is D, L, S, or Y.
- ⁇ 5 is S
- ⁇ 3 is V or Y
- ⁇ 4 is G or V
- ⁇ 6 is D or S.
- ⁇ 3 when ⁇ 3 is A; ⁇ 4 is Y; ⁇ 5 is L; and ⁇ 6 is Y. In some aspects, when ⁇ 3 is L; ⁇ 4 is P; ⁇ 5 is F; and ⁇ 6 is L. In some aspects, when ⁇ 3 is Y; ⁇ 4 is V; ⁇ 5 is S; and ⁇ 6 is D. In some aspects, when ⁇ 3 is V; ⁇ 4 is G; ⁇ 5 is S; and ⁇ 6 is S.
- the antibody comprises a CDR-L2 sequence defined by the consensus sequence ⁇ 1 -A-S- ⁇ 4 -R-A- ⁇ 7 (SEQ ID NOS: 128, 130, 132, 134-138, 143, and 145), where ⁇ 1 is D or G; ⁇ 4 is A, D, N, R, S, T, or Y; and ⁇ 7 is A, N, S, or T.
- ⁇ 1 when ⁇ 1 is G; ⁇ 4 is A, D, N, R, S, T, or Y; and ⁇ 7 is A, N, or T.
- ⁇ 1 when ⁇ 1 is D; ⁇ 4 is S or T; and ⁇ 7 is S or T.
- when ⁇ 4 is S; ⁇ 1 is G or D; and ⁇ 7 is S or T.
- when ⁇ 4 is N; ⁇ 1 is G or D; and ⁇ 7 is A or T.
- ⁇ 4 when ⁇ 4 is T; ⁇ 1 is G or D; and ⁇ 7 is T.
- ⁇ 7 when ⁇ 7 is T; ⁇ 1 is G or D; and ⁇ 4 is A, N, R, S, T, or Y.
- ⁇ 1 when ⁇ 1 is G; ⁇ 4 is Y; and ⁇ 7 is T. In some aspects, when ⁇ 1 is G; ⁇ 4 is R; and ⁇ 7 is T. In some aspects, when ⁇ 1 is G; ⁇ 4 is T; and ⁇ 7 is T.
- the antibody comprises a CDR-L1 sequence defined by the consensus sequence ⁇ 1 -A-S-Q- ⁇ 5 -V-S-S- ⁇ 9 - ⁇ 10 -L-A (SEQ ID NOS: 105-112 and 117), where ⁇ 1 is E, G, K, Q, or R; ⁇ 5 is A or S; ⁇ 9 is A, D, N, S, or T; and ⁇ 10 is F or Y.
- ⁇ 1 when ⁇ 1 is R; ⁇ 5 is Q or S; ⁇ 9 is A, S, or T; and ⁇ 10 is S or Y.
- ⁇ 1 when ⁇ 1 is G; ⁇ 5 is Q or S; ⁇ 9 is A or D; and ⁇ 10 is F or Y.
- ⁇ 1 when ⁇ 1 is Q; ⁇ 5 is A or S; ⁇ 9 is N or S; and ⁇ 10 is Y.
- ⁇ 5 when ⁇ 5 is S; ⁇ 1 is E, G, Q, or R; ⁇ 9 is A, D, S, or T; and ⁇ 10 is F or Y.
- ⁇ 5 when ⁇ 5 is A; ⁇ 1 is K or Q; ⁇ 9 is N or S; and ⁇ 10 is Y.
- ⁇ 9 when ⁇ 9 is S; ⁇ 1 is E, K, Q, or R; ⁇ 5 is A or S; and ⁇ 10 is Y.
- ⁇ 9 when ⁇ 9 is A; ⁇ 1 , is G or R; ⁇ 5 is S; and ⁇ 10 is F or Y.
- ⁇ 1 when ⁇ 1 is R; ⁇ 5 is S; ⁇ 9 is S; and ⁇ 10 is Y. In some aspects, when ⁇ 1 is G; ⁇ 5 is S; ⁇ 9 is D; and ⁇ 10 is Y. In some aspects, when ⁇ 1 is Q; ⁇ 5 is A; ⁇ 9 is N; and ⁇ 10 is Y. In some aspects, when ⁇ 1 is G; ⁇ 5 is S; ⁇ 9 is A; and ⁇ 10 is F. In some aspects, when ⁇ 1 is R; ⁇ 5 is S; ⁇ 9 is T; and ⁇ 10 is Y. In some aspects, when ⁇ 1 is Q; ⁇ 5 is S; ⁇ 9 is S: and ⁇ 10 is Y.
- ⁇ 1 when ⁇ 1 is K; ⁇ 5 is A; ⁇ 9 is S; and ⁇ 10 is Y. In some aspects, when ⁇ 1 is E; ⁇ 5 is S; ⁇ 9 is S; and ⁇ 10 is Y. In some aspects, when ⁇ 1 is R; ⁇ 5 is S; ⁇ 9 is A; and ⁇ 10 is Y.
- the antibody comprises a CDR-L1 sequence defined by the consensus sequence R-A-S-Q-S- ⁇ 6 - ⁇ 7 -S- ⁇ 9 -L- ⁇ 11 (SEQ ID NOS: 119 and 123-124), where ⁇ 6 is I or V; ⁇ 7 is N or S; ⁇ 9 is N, W, or Y; ⁇ 11 is A or N.
- ⁇ 6 when ⁇ 6 is I, ⁇ 7 is N or S; ⁇ 9 is W or Y; and ⁇ 11 is A or N. In some aspects, when ⁇ 7 is S, ⁇ 6 is I or V; ⁇ 9 is N or Y: and ⁇ 11 is A or N. In some aspects, when ⁇ 11 is A, ⁇ 6 is I or V; ⁇ 7 is N or S; and ⁇ 9 is N or W.
- ⁇ 6 when ⁇ 6 is I; ⁇ 7 is N; ⁇ 9 is W; and ⁇ 11 is A. In some aspects, when ⁇ 6 is I; ⁇ 7 is S; ⁇ 9 is Y; and ⁇ 11 is N. In some aspects, when ⁇ 6 is V; ⁇ 7 is S; ⁇ 9 is N; and ⁇ 11 is A.
- the antibody comprises a CDR-L1 sequence defined by the consensus sequence ⁇ 1 - ⁇ 2 -S-Q-S-V-S- ⁇ 8 - ⁇ 9 -Y-L-A (SEQ ID NOS: 113-116), where ⁇ 1 is E or R; ⁇ 2 is A or V; F is A or V; ⁇ 8 is A, D, or S; and ⁇ 10 is A or S.
- ⁇ 1 is E; ⁇ 2 is A or V; ⁇ 8 is A or S; and ⁇ 9 is A or S.
- ⁇ 2 is A; ⁇ 1 is E; ⁇ 8 is A or S; and ⁇ 9 is A or S.
- ⁇ 2 is V; ⁇ 1 is E or R; ⁇ 8 A or D; and ⁇ 9 is A or S.
- ⁇ 8 is A; ⁇ 1 is E; ⁇ 2 is A or V; and ⁇ 9 is S.
- ⁇ 9 is S; ⁇ 1 is E; ⁇ 2 is A or V; and ⁇ 8 is A.
- ⁇ 9 is A; ⁇ 1 is E or R; ⁇ 2 is A or V; and ⁇ 8 D or S.
- ⁇ 1 when ⁇ 1 is E; ⁇ 2 is A; ⁇ 8 is A; and ⁇ 9 is S. In some aspects, when ⁇ 1 is E; ⁇ 2 is A; ⁇ 8 is S; and ⁇ 9 is A. In some aspects, when ⁇ 1 is R; ⁇ 2 is V; ⁇ 8 is A; and ⁇ 9 is A. In some aspects, when ⁇ 1 is E; ⁇ 2 is V; ⁇ 8 is A; and ⁇ 9 is S.
- the antibody that specifically binds HLA-G is an antibody comprising a variable region that is encoded by a particular germline, gene, or a variant thereof.
- the illustrative antibodies provided herein comprise variable regions that are encoded by the heavy chain variable region germline genes V H 3-23, V H 4-39, V H 3-11, and V H 4-0B or variants thereof; and the light chain variable region germline genes VK1-33, VK3-20, VK1-12, and VK1-05 or variants thereof.
- the CDR sequences provided herein may also be useful when combined with variable regions encoded by other variable region germline genes or variants thereof.
- the CDR sequences provided herein may be useful when combined with variable regions encoded by variable region germline genes, or variants thereof, that are structurally similar to the variable region germline genes recited above.
- a CDR-H sequence provided herein may be combined with a variable region encoded by a variable region germline gene selected from the V H 1 or V H 3 family, or a variant thereof.
- a CDR-L sequence provided herein may be combined with a variable region encoded by a variable region germline gene selected from the V ⁇ 3, V ⁇ 1, V ⁇ 3, and V ⁇ 4 families, or a variant thereof.
- the affinity of the antibody for HLA-G is less than about 10 ⁇ 5 M, less than about 10 ⁇ 6 M, less than about 10 ⁇ 7 M, less than about 10 ⁇ 8 M, less than about 10 ⁇ 9 M, less than about 10 ⁇ 10 M, less than about 10 ⁇ 11 M, or less than about 10 ⁇ 12 M.
- the affinity of the antibody is between about 10 ⁇ 7 M and 10 ⁇ 11 M. In some embodiments, the affinity of the antibody is between about 10 ⁇ 7 M and 10 ⁇ 11 M. In some embodiments, the affinity of the antibody is between about 10 ⁇ 7 M and 10 ⁇ 9 M.
- the affinity of the antibody is between about 10 ⁇ 7 M and 10 ⁇ 8 M. In some embodiments, the affinity of the antibody is between about 10 ⁇ 8 M and 10 ⁇ 11 M. In some embodiments, the affinity of the antibody is between about 10 ⁇ 8 M and 10 ⁇ 11 M. In some embodiments, the affinity of the antibody is between about 10 ⁇ 9 M and 10 ⁇ 11 M. In some embodiments, the affinity of the antibody is between about 10 ⁇ 10 M and 10 ⁇ 11 M.
- the affinity of the antibody for human HLA-G is between about 1.00 ⁇ 10 ⁇ 8 M and 9.43 ⁇ 10 ⁇ 10 M. In some embodiment, the affinity of the antibody for human HLA-G is about 1.00 ⁇ 10 ⁇ 8 M, about 1.08 ⁇ 10 ⁇ 8 M, about 1.10 ⁇ 10 ⁇ 8 M, about 1.13 ⁇ 10 ⁇ 8 M, about 1.14 ⁇ 10 ⁇ 8 M, about 1.16 ⁇ 10 ⁇ 8 M, about 1.29 ⁇ 10 ⁇ 8 M, about 1.40 ⁇ 10 ⁇ 8 M, about 1.41 ⁇ 10 ⁇ 8 M, about 1.46 ⁇ 10 ⁇ 8 M, about 1.67 ⁇ 10 ⁇ 8 M, about 1.79 ⁇ 10 ⁇ 8 M, about 1.81 ⁇ 10 ⁇ 8 M, about 2.04 ⁇ 10 ⁇ 8 M, about 2.30 ⁇ 10 ⁇ 8 M, about 2.49 ⁇ 10 ⁇ 8 M, about 2.59 ⁇ 10 ⁇ 8 M, about 2.94 ⁇ 10 ⁇ 8 M, about 2.95 ⁇ 10 ⁇ 8 M, about 3.11 ⁇ 10 ⁇ 8 M, about 3.
- the antibody has a k when associating with human HLA-G of between about 1.41 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 and about 1.07 ⁇ 10 6 M ⁇ 1 ⁇ sec ⁇ 1 . In some embodiments the antibody has a k on when associating with human HLA-G of about 1.41 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 1.49 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 1.66 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 2.90 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 3.60 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 3.74 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 3.78 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 4.03 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 4.30 ⁇ 10 5 M ⁇ 1 ⁇ sec ⁇ 1 , about 4.32 ⁇ 10 5 M ⁇ 1 ⁇
- the antibody has a k off when associating with human HLA-G of between about 1.06 ⁇ 10 2 sec ⁇ 1 and about 8.55 ⁇ 10 5 sec ⁇ 1 . In some embodiments the antibody has a k off of about 1.06 ⁇ 10 ⁇ 2 sec ⁇ 1 , about 1.13 ⁇ 10 ⁇ 2 sec ⁇ 1 , about 1.87 ⁇ 10 ⁇ 2 sec ⁇ 1 , about 2.13 ⁇ 10 ⁇ 2 sec ⁇ 1 , about 3.62 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 3.66 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 3.75 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 3.78 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 3.83 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 3.96 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 4.17 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 4.27 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 4.29 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 4.41 ⁇ 10 ⁇ 3 sec ⁇ 1 , about 1.
- the K D , k a , and k d are determined at 25° C. In some embodiments, the K D , k a , and k d are determined by surface plasmon resonance. In some embodiments, the K D , k a , and k d are determined according to the methods described in the examples.
- the antibody decreases the affinity of HLA-G for its ligand(s). In some aspects, the antibody disrupts the association of HLA-G with beta-2-microglobulin and/or its cognate peptide. In some aspects the antibody prevents HLA-G dimerization or oligomizeration.
- the antibody inhibits HLA-G function on tumor cells. In some aspects, the antibody inhibits HLA-G function on immune cells. In some embodiments, the antibody blocks HLA-G interaction and/or binding to an ITIM inhibitory receptor. In some embodiments, the antibody blocks HLA-G interaction and/or binding to ILT2. In some embodiments, the antibody blocks HLA-G interaction and/or binding to ILT4. In some embodiments, the antibody blocks HLA-G interaction and/or binding to KIR2DL4.
- the antibody inhibits immune suppressive function. In some embodiments, the antibody inhibits HLA-G mediated suppression of NK cells. In some embodiments, the antibody inhibits HLA-G mediated suppression of cytotoxic T lymphocytes. In some embodiments, the antibody inhibits HLA-G mediated suppression of B cells. In some embodiments, the antibody inhibits HLA-G mediated suppression of neutrophils. In some embodiments, the antibody inhibits HLA-G mediated suppression of dendritic cells. In some embodiments, the antibody inhibits HLA-G mediated suppression of macrophages. In some embodiments, the antibody inhibits HLA-G mediated suppression of monocytes. In some embodiments, the antibody inhibits HLA-G mediated suppression of NK and/or T cell cytolysis and/or proliferation.
- the antibody prevents or inhibits HLA-G mediated suppression of phagocytosis. In some embodiments, the antibody mediates HLA-G mediated induction of T regulatory cells. In some embodiments, the antibody prevents or inhibits the generation or expansion of regulatory T cells. In some embodiments, the antibody inhibits tumor growth by antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis (ADCP).
- ADCC antibody-dependent cellular cytotoxicity
- ADCP phagocytosis
- the decrease is about or less than a 10% decrease, about or less than a 20% decrease, about or less than a 30% decrease, about or less than a 40% decrease, about or less than a 50% decrease, about or less than a 60% decrease, about or less than a 70% decrease, about or less than an 80% decrease, about or less than a 90% decrease, or about a complete decrease.
- the increase is about or greater than a 10% increase, about or greater than a 20% increase, about or greater than a 30% increase, about or greater than a 40% increase, about or greater than a 50% increase, about or greater than a 60% increase, about or greater than a 70% increase, about or greater than an 80% increase, about or greater than a 90% increase, or a complete increase.
- the antibody binds to an epitope of HLA-G.
- An epitope often consists of a number of contiguous amino acids such as, for example, without limitation, 5-6 amino acids.
- the epitope comprises or consists of contiguous or non-contiguous amino acids.
- the contiguous or non-contiguous amino acids are within a domain of HLA-G.
- the domain comprises or consists of an alpha three domain.
- HLA-G has a sequence identical to the amino acid sequence set forth in SEQ ID NO: 342.
- the epitope has an amino acid sequence that is within the amino acid sequence set forth in SEQ ID NO: 342. In some aspects, the epitope has an amino acid sequence that is 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% identical to a sequence that is within the sequence set forth in SEQ ID NO: SEQ ID NO: 342.
- the epitope comprises or consists of a contiguous or non-contiguous span of amino acids including residues 195, 197, and/or 198 of the sequence set forth in SEQ ID NO: 342. In some aspects, the epitope comprises a sequence that is identical or corresponds to residues 195, 197, and/or 198 of a sequence that is within the sequence set forth in SEQ ID NO: 342. In some aspects, the epitope has a sequence that has a 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% identity to a sequence that is within the sequence set forth in SEQ ID NO: 342.
- the epitope has 1, 2, 3, 4, 5, 6, 7, 8, or 9 substitutions from a sequence that is within the sequence set forth in forth in SEQ ID NO: 342. In some aspects, the epitope has 1, 2 or 3 substitutions from residues a sequence that is within the sequence set forth in SEQ ID NO: 342. In some aspects, the antibody makes contact with any of the residues set forth in FIG. 9 .
- the antibody competes with any of the antibodies set forth herein. Competition could be, for example, without limitation, binding competition, inhibition competition, or any other form of competition. In some aspects, the antibody competes with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 of antibodies 38410, 38418, 38422, 38426, 38381, 38358, 37323, 38373, 38375, 38379, 38389, 33303, or 33357. In some aspects, the antibody competes with any of the antibodies set forth in FIG. 2 or FIG. 3 . In some aspects, the antibody competes with 1, 2, 3, 4, 5, 6, 7, or 8 of 38373, 38375, 38379, 38418, 38422, 38426, 38410 or 38381.
- the antibody competes with 38358. In some aspects, the antibody competes with 1, 2, 3, 4, 5, 6, 7, 8, or 9 of 38373, 38375, 38379, 38418, 38422, 38426, 38410 or 38381, or 38358. In some aspects, the antibody competes with one or both of 37323 and/or 38389. In some aspects, the antibody competes with one or both of 33303 and/or 33357.
- an antibody may be altered to increase, decrease or eliminate the extent to which it is glycosylated. Glycosylation of polypeptides is typically either “N-linked” or “O-linked.”
- N-linked glycosylation refers to the attachment of a carbohydrate moiety to the side chain of an asparagine residue.
- the tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain.
- X is any amino acid except proline
- O-linked glycosylation refers to the attachment of one of the sugars N-acetylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.
- Addition or deletion of N-linked glycosylation sites to the antibody may be accomplished by altering the amino acid sequence such that one or more of the above-described tripeptide sequences is created or removed.
- Addition or deletion of O-linked glycosylation sites may be accomplished by addition, deletion, or substitution of one or more serine or threonine residues in or to (as the case may be) the sequence of an antibody.
- the antibody is glycosylated. In certain embodiments, the antibody is deglycosylated. Carbohydrates may be removed by standard techniques. In certain embodiments, the antibody is aglycosylated, for instance by expression in a system that does not glycosylate.
- amino acid modifications may be introduced into the Fc region of an antibody provided herein to generate an Fc region variant.
- the Fc region variant possesses some, but not all, effector functions.
- Such antibodies may be useful, for example, in applications in which the half-life of the antibody in vivo is important, yet certain effector functions are unnecessary or deleterious.
- effector functions include complement-dependent cytotoxicity (CDC) and antibody-directed complement-mediated cytotoxicity (ADCC). Numerous substitutions or substitutions or deletions with altered effector function are known in the art.
- the Fc is modified.
- a hinge of an IgG1 or IgG4 antibody is modified. Modification of a hinge region stabilizes an antibody and prevents formation of unwanted bispecific antibodies.
- the modification comprises an L234A, L235A, and/or G237A according to a Kabat numbering scheme or residues number 117, 118, and 120, respectively, wherein residues are numbered according to any of SEQ ID NO: 334.
- the modification comprises an EU S228P or an S241P according to a Kabat numbering scheme or number 108 according to SEQ ID NO: 335.
- an IgG Fc is engineered to modulate antibody effector function (See Wang et al., Protein Cell, 2018, January; 9(1): 63-73), which is incorporated by reference herein in its entirety, including any drawings).
- Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest are provided in U.S. Pat. Nos. 5,500,362 and 5,821,337; Hellstrom et al., Proc. Natl. Acad. Sci. U.S.A., 1986, 83:7059-7063; Hellstrom et al., Proc. Natl. Acad. Sci. U.S.A., 1985, 82:1499-1502; and Bruggemann et al., J. Exp. Med., 1987, 166:1351-1361.
- Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells.
- ADCC activity of the molecule of interest may be assessed in vivo, using an animal model such as that disclosed in Clynes et al. Proc. Natl. Acad. Sci. U.S.A., 1998, 95:652-656.
- C1q binding assays may also be carried out to confirm that the antibody is unable to bind C1q and hence lacks CDC activity.
- Examples of C1q binding assays include those described in WO 2006/029879 and WO 2005/100402.
- Complement activation assays include those described, for example, in Gazzano-Santoro et al., J. Immunol. Methods, 1996, 202:163-171; Cragg et al., Blood, 2003, 101:1045-1052; and Cragg and Glennie, Blood, 2004, 103:2738-2743.
- FcRn binding and in vivo clearance can also be measured, for example, using the methods described in Petkova et al., Intl. Immunol., 2006, 18:1759-1769.
- the HLA-G antigen to be used for production of antibodies may be intact HLA-G or a fragment of HLA-G.
- the intact HLA-G, or fragment of HLA-G may be in the form of an isolated protein or expressed by a cell.
- Other forms of HLA-G useful for generating antibodies will be apparent to those skilled in the art.
- Monoclonal antibodies may be obtained, for example, using the hybridoma method first described by Kohler et al., Nature, 1975, 256:495-497, and/or by recombinant DNA methods (see e.g., U.S. Pat. No. 4,816,567). Monoclonal antibodies may also be obtained, for example, using phage or yeast-based libraries. See e.g., U.S. Pat. Nos. 8,258,082 and 8,691,730.
- lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization.
- lymphocytes may be immunized in vitro. Lymphocytes are then fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell.
- a suitable fusing agent such as polyethylene glycol
- the hybridoma cells are seeded and grown in a suitable culture medium that contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
- a suitable culture medium that contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
- the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.
- Useful myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive media conditions, such as the presence or absence of HAT medium.
- preferred myeloma cell lines are murine myeloma lines, such as those derived from MOP-21 and MC-11 mouse tumors (available from the Salk Institute Cell Distribution Center, San Diego, Calif.), and SP-2 or X63-Ag8-653 cells (available from the American Type Culture Collection, Rockville, Md.).
- Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies. See e.g., Kozbor, J. Immunol. 1984, 133:3001.
- hybridoma cells After the identification of hybridoma cells that produce antibodies of the desired specificity, affinity, and/or biological activity, selected clones may be subcloned by limiting dilution procedures and grown by standard methods. See Goding, supra. Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal.
- DNA encoding the monoclonal antibodies may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies).
- the hybridoma cells can serve as a useful source of DNA encoding antibodies with the desired properties.
- the DNA may be placed into expression vectors, which are then transfected into host cells such as bacteria (e.g., E. coli ), yeast (e.g., Saccharomyces or Pichia sp.), COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce antibody, to produce the monoclonal antibodies.
- Humanized antibodies may be generated by replacing most, or all, of the structural portions of a monoclonal antibody with corresponding human antibody sequences. Consequently, a hybrid molecule is generated in which only the antigen-specific variable, or CDR, is composed of non-human sequence.
- Methods to obtain humanized antibodies include those described in, for example, Winter and Milstein, Nature, 1991, 349:293-299; Rader et al., Proc. Nat. Acad. Sci. U.S.A., 1998, 95:8910-8915; Steinberger et al., J. Biol. Chem., 2000. 275:36073-36078; Queen et al., Proc. Natl. Acad. Sci. U.S.A., 1989, 86:10029-10033; and U.S. Pat. Nos. 5,585,089, 5,693,761, 5,693,762, and 6,180,370.
- Human antibodies can be generated by a variety of techniques known in the art, for example by using transgenic animals (e.g., humanized mice). See, e.g., Jakobovits et al., Proc. Natl. Acad. Sci. U.S.A., 1993, 90:2551; Jakobovits et al., Nature, 1993, 362:255-258; Bruggermann et al., Year in Immuno., 1993, 7:33; and U.S. Pat. Nos. 5,591,669, 5,589,369 and 5,545,807. Human antibodies can also be derived from phage-display libraries (see e.g., Hoogenboom et al., J. Mol.
- Human antibodies may also be generated by in vitro activated B cells (see e.g., U.S. Pat. Nos. 5,567,610 and 5,229,275). Human antibodies may also be derived from yeast-based libraries (see e.g., U.S. Pat. No. 8,691,730).
- the invention also provides isolated nucleic acids encoding anti-HLA-G antibodies, vectors and host cells comprising the nucleic acids and recombinant techniques for the production of the antibodies.
- the nucleic acid encoding it may be isolated and inserted into a replicable vector for further cloning (i.e., amplification of the DNA) or expression.
- the nucleic acid may be produced by homologous recombination, for example as described in U.S. Pat. No. 5,204,244.
- the vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence, for example as described in U.S. Pat. No. 5,534,615.
- Suitable host cells include any prokaryotic (e.g., bacterial), lower eukaryotic (e.g., yeast), or higher eukaryotic (e.g., mammalian) cells.
- Suitable prokaryotes include cubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as Escherichia ( E. coli ), Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella ( S. typhimurium ), Serratia ( S. marcescans ), Shigella, Bacilli ( B. subtilis and B. licheniformis ), Pseudomonas ( P.
- prokaryotic e.g., bacterial
- lower eukaryotic e.g., yeast
- higher eukaryotic e.g., mammalian cells.
- Suitable prokaryotes include cubacteria, such as Gram-negative or Gram-positive organism
- E. coli 294 One useful E. coli cloning host is E. coli 294, although other strains such as E. coli B, E. coli X1776, and E. coli W3110 are suitable.
- eukaryotic microbes such as filamentous fungi or yeast are also suitable cloning or expression hosts for anti-HLA-G antibody-encoding vectors.
- Saccharomyces cerevisiae or common baker's yeast, is a commonly used lower eukaryotic host microorganism.
- Schizosaccharomyces pombe Kluyveromyces ( K. lactis, K. fragilis, K. bulgaricus, K. wickeramii, K. waltii, K. drasophilarum, K. thermotolerans , and K.
- Useful mammalian host cells include COS-7 cells, HEK293 cells; baby hamster kidney (BHK) cells; Chinese hamster ovary (CHO); mouse sertoli cells; African green monkey kidney cells (VERO-76), and the like.
- the host cells used to produce the anti-HLA-G antibody of this invention may be cultured in a variety of media.
- Commercially available media such as, for example, Ham's F10, Minimal Essential Medium (MEM), RPMI-1640, and Dulbecco's Modified Eagle's Medium (DMEM) are suitable for culturing the host cells.
- MEM Minimal Essential Medium
- RPMI-1640 RPMI-1640
- DMEM Dulbecco's Modified Eagle's Medium
- any of the media described in Ham et al., Meth. Enz., 1979, 58:44; Barnes et al., Anal. Biochem., 1980, 102:255; and U.S. Pat. Nos. 4,767,704, 4,657,866, 4,927,762, 4,560,655, and 5,122,469, or WO 90/03430 and WO 87/00195 may be used.
- any of these media may be supplemented as necessary with hormones and/or other growth factors (such as insulin, transferrin, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics, trace elements (defined as inorganic compounds usually present at final concentrations in the micromolar range), and glucose or an equivalent energy source. Any other necessary supplements may also be included at appropriate concentrations that would be known to those skilled in the art.
- growth factors such as insulin, transferrin, or epidermal growth factor
- salts such as sodium chloride, calcium, magnesium, and phosphate
- buffers such as HEPES
- nucleotides such as adenosine and thymidine
- antibiotics such as adenosine and thymidine
- trace elements defined as inorganic compounds usually present at final concentrations in the micromolar range
- the culture conditions such as temperature, pH, and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.
- the antibody can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the antibody is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration.
- the particulate debris either host cells or lysed fragments
- the particulate debris is removed, for example, by centrifugation or ultrafiltration.
- Carter et al. Bio/Technology, 1992, 10:163-167 describes a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli . Briefly, cell paste is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF) over about 30 minutes. Cell debris can be removed by centrifugation.
- sodium acetate pH 3.5
- EDTA EDTA
- PMSF phenylmethylsulf
- the antibody is produced in a cell-free system.
- the cell-free system is an in vitro transcription and translation system as described in Yin et al., mAbs, 2012, 4:217-225, incorporated by reference in its entirety.
- the cell-free system utilizes a cell-free extract from a eukaryotic cell or from a prokaryotic cell.
- the prokaryotic cell is E. coli .
- Cell-free expression of the antibody may be useful, for example, where the antibody accumulates in a cell as an insoluble aggregate, or where yields from periplasmic expression are low.
- supernatants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon® or Millipore® Pellcon® ultrafiltration unit.
- a protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants.
- the antibody composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being a particularly useful purification technique.
- the suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain that is present in the antibody.
- Protein A can be used to purify antibodies that are based on human ⁇ 1, ⁇ 2, or ⁇ 4 heavy chains (Lindmark et al., J. Immunol. Meth., 1983, 62:1-13).
- Protein G is useful for all mouse isotypes and for human ⁇ 3 (Guss et al., EMBO J., 1986, 5:1567-1575).
- the matrix to which the affinity ligand is attached is most often agarose, but other matrices are available.
- Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose.
- the antibody comprises a C H3 domain
- the BakerBond ABX® resin is useful for purification.
- the mixture comprising the antibody of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH between about 2.5 to about 4.5, generally performed at low salt concentrations (e.g., from about 0 to about 0.25 M salt).
- Suitable routes of administration include, but are not limited to, the inhalation, intra-arterial, intradermal, intramuscular, intraperitoneal, intravenous, nasal, parenteral, pulmonary, and subcutaneous routes.
- the pharmaceutical composition may comprise one or more pharmaceutical excipients. Any suitable pharmaceutical excipient may be used, and one of ordinary skill in the art is capable of selecting suitable pharmaceutical excipients. Accordingly, the pharmaceutical excipients provided below are intended to be illustrative, and not limiting. Additional pharmaceutical excipients include, for example, those described in the Handbook of Pharmaceutical Excipients , Rowe et al. (Eds.) 6th Ed. (2009), incorporated by reference in its entirety.
- the pharmaceutical composition comprises an anti-foaming agent.
- Any suitable anti-foaming agent may be used.
- the anti-foaming agent is selected from an alcohol, an ether, an oil, a wax, a silicone, a surfactant, and combinations thereof.
- the anti-foaming agent is selected from a mineral oil, a vegetable oil, ethylene bis stearamide, a paraffin wax, an ester wax, a fatty alcohol wax, a long chain fatty alcohol, a fatty acid soap, a fatty acid ester, a silicon glycol, a fluorosilicone, a polyethylene glycol-polypropylene glycol copolymer, polydimethylsiloxane-silicon dioxide, ether, octyl alcohol, capryl alcohol, sorbitan trioleate, ethyl alcohol, 2-ethyl-hexanol, dimethicone, oleyl alcohol, simethicone, and combinations thereof.
- the pharmaceutical composition comprises a cosolvent.
- cosolvents include ethanol, poly(ethylene) glycol, butylene glycol, dimethylacetamide, glycerin, and propylene glycol.
- the pharmaceutical composition comprises a buffer.
- buffers include acetate, borate, carbonate, lactate, malate, phosphate, citrate, hydroxide, diethanolamine, monoethanolamine, glycine, methionine, guar gum, and monosodium glutamate.
- the pharmaceutical composition comprises a carrier or filler.
- carriers or fillers include lactose, maltodextrin, mannitol, sorbitol, chitosan, stearic acid, xanthan gum, and guar gum.
- the pharmaceutical composition comprises a surfactant.
- surfactants include d-alpha tocopherol, benzalkonium chloride, benzethonium chloride, cetrimide, cetylpyridinium chloride, docusate sodium, glyceryl behenate, glyceryl monooleate, lauric acid, macrogol 15 hydroxystearate, myristyl alcohol, phospholipids, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, polyoxylglycerides, sodium lauryl sulfate, sorbitan esters, and vitamin E polyethylene(glycol) succinate.
- the pharmaceutical composition comprises an anti-caking agent.
- anti-caking agents include calcium phosphate (tribasic), hydroxymethyl cellulose, hydroxypropyl cellulose, and magnesium oxide.
- excipients that may be used with the pharmaceutical compositions include, for example, albumin, antioxidants, antibacterial agents, antifungal agents, bioabsorbable polymers, chelating agents, controlled release agents, diluents, dispersing agents, dissolution enhancers, emulsifying agents, gelling agents, ointment bases, penetration enhancers, preservatives, solubilizing agents, solvents, stabilizing agents, and sugars. Specific examples of each of these agents are described, for example, in the Handbook of Pharmaceutical Excipients , Rowe et al. (Eds.) 6th Ed. (2009), The Pharmaceutical Press, incorporated by reference in its entirety.
- the pharmaceutical composition comprises a solvent.
- the solvent is saline solution, such as a sterile isotonic saline solution or dextrose solution.
- the solvent is water for injection.
- the pharmaceutical compositions are in a particulate form, such as a microparticle or a nanoparticle.
- Microparticles and nanoparticles may be formed from any suitable material, such as a polymer or a lipid.
- the microparticles or nanoparticles are micelles, liposomes, or polymersomes.
- a composition provided herein is a pharmaceutical composition or a single unit dosage form.
- Pharmaceutical compositions and single unit dosage forms provided herein comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic antibodies.
- anhydrous pharmaceutical compositions and dosage forms comprising an antibody, since water can facilitate the degradation of some antibodies.
- Anhydrous pharmaceutical compositions and dosage forms provided herein can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions.
- Pharmaceutical compositions and dosage forms that comprise lactose and at least one active ingredient that comprises a primary or secondary amine can be anhydrous if substantial contact with moisture and/or humidity during manufacturing, packaging, and/or storage is expected.
- anhydrous pharmaceutical composition should be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions can be packaged using materials known to prevent exposure to water such that they can be included in suitable formulary kits. Examples of suitable packaging include, but are not limited to, hermetically scaled foils, plastics, unit dose containers (e.g., vials), blister packs, and strip packs.
- the pharmaceutical composition further comprises one or both of an antibody to an immune inhibitory receptor or ligand and/or an antibody to an immune stimulatory receptor and/or ligand.
- the pharmaceutical composition further comprises an effective amount of at least one of the following: an anti-ILT2 antibody; an anti-ILT-4 antibody; an anti-ILT4 antibody; an anti-KIR2DL4 antibody; an anti-HLA-E antibody; an anti-NKG2A antibody; an anti-HLA-F antibody; an anti-PD-L1 antibody; an anti-PD-1 antibody; an anti-CTLA4 antibody; an anti-CD38 antibody; an anti-CD73 antibody; an anti-A2A receptor antibody; an anti-A2B receptor antibody; an anti-A2A/A2B dual receptor antibody or a combination thereof; an anti-CD39 antibody; an anti-CD73 antibody; an anti-CD47 antibody; and/or a small molecule inhibitor.
- the pharmaceutical composition further comprises an anti-Tim-3 antibody: an anti-TIGIT antibody; an anti-Vista antibody; an anti-CD94 antibody; an anti-ILT2 antibody, an anti-ILT4 antibody, an anti-PD-L1 antibody, and/or an anti-CD47 antibody; a small molecule inhibitor; a bi-specific T cell engager, CAR-T therapy, CAR-NK therapy, CAR-Macrophage therapy, engineered cell therapy, and/or adaptive T cell therapy; an oncolytic virus; a chemotherapy; and/or an ADCC capable therapy using effector competent antibodies such as anti-CD19, anti-CD20, anti-EGFR, anti-Her2, anti-SLAMF7, anti-CD52, anti-BCMA, anti-GD2, anti-CD38, and/or anti-CCR4.
- ADCC capable therapy is enhanced ADCC capable therapy.
- the effector is enhanced through afucosylation, point mutations, or another method.
- parenteral dosage forms can be administered to subjects by various routes including, but not limited to, subcutaneous, intravenous (including bolus injection), intramuscular, and intra-arterial. Because their administration typically bypasses subjects' natural defenses against contaminants, parenteral dosage forms are typically, sterile or capable of being sterilized prior to administration to a subject. Examples of parenteral dosage forms include, but are not limited to, solutions ready for injection, dry products ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions.
- Suitable vehicles that can be used to provide parenteral dosage forms are well known to those skilled in the art. Examples include, but are not limited to: Water for Injection USP; aqueous vehicles such as, but not limited to, Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, and Lactated Ringer's Injection; water miscible vehicles such as, but not limited to, ethyl alcohol, polyethylene glycol, and polypropylene glycol; and non-aqueous vehicles such as, but not limited to, corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate.
- aqueous vehicles such as, but not limited to, Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, and Lactated Ringer's Injection
- Excipients that increase the solubility of one or more of the antibodies disclosed herein can also be incorporated into the parenteral dosage forms.
- the doctor will determine the posology which he considers most appropriate according to a preventive or curative treatment and according to the age, weight, condition and other factors specific to the subject to be treated.
- the amount of the antibody or composition which will be effective in the prevention or treatment of a disorder or one or more symptoms thereof will vary with the nature and severity of the disease or condition, and the route by which the antibody is administered.
- the frequency and dosage will also vary according to factors specific for each subject depending on the specific therapy (e.g., therapeutic or prophylactic agents) administered, the severity of the disorder, disease, or condition, the route of administration, as well as age, body, weight, response, and the past medical history of the subject.
- Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.
- exemplary doses of a composition include milligram or microgram amounts of the antibody per kilogram of subject or sample weight (e.g., about 10 micrograms per kilogram to about 50 milligrams per kilogram, about 100 micrograms per kilogram to about 25 milligrams per kilogram, or about 100 microgram per kilogram to about 10 milligrams per kilogram).
- the dosage of the antibody provided herein, based on weight of the antibody, administered to prevent, treat, manage, or ameliorate a disorder, or one or more symptoms thereof in a subject is 0.1 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 10 mg/kg, or 15 mg/kg or more of a subject's body weight.
- the dosage of the composition or a composition provided herein administered to prevent, treat, manage, or ameliorate a disorder, or one or more symptoms thereof in a subject is 0.1 mg to 200 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 0.1 mg to 20 mg, 0.1 mg to 15 mg, 0.1 mg to 10 mg, 0.1 mg to 7.5 mg, 0.1 mg to 5 mg, 0.1 to 2.5 mg, 0.25 mg to 20 mg, 0.25 to 15 mg, 0.25 to 12 mg, 0.25 to 10 mg, 0.25 mg to 7.5 mg, 0.25 mg to 5 mg, 0.25 mg to 2.5 mg, 0.5 mg to 20 mg, 0.5 to 15 mg, 0.5 to 12 mg, 0.5 to 10 mg, 0.5 mg to 7.5 mg, 0.5 mg to 5 mg, 0.5 mg to 2.5 mg, 1 mg to 20 mg, 1 mg to 15 mg, 1 mg to 12 mg, 1 mg to 10 mg, 1 mg to 7.5 mg, 1 mg to 5 mg, or 1 mg to 2.5 mg.
- the dose can be administered according to a suitable schedule, for example, once, two times, three times, or for times weekly. It may be necessary to use dosages of the antibody outside the ranges disclosed herein in some cases, as will be apparent to those of ordinary skill in the art. Furthermore, it is noted that the clinician or treating physician will know how and when to interrupt, adjust, or terminate therapy in conjunction with subject response.
- dosage amounts and dose frequency schedules are also encompassed by the herein described dosage amounts and dose frequency schedules.
- the dosage administered to the subject may be increased to improve the prophylactic or therapeutic effect of the composition or it may be decreased to reduce one or more side effects that a particular subject is experiencing.
- treatment or prevention can be initiated with one or more loading doses of an antibody or composition provided herein followed by one or more maintenance doses.
- a dose of an antibody or composition provided herein can be administered to achieve a steady-state concentration of the antibody in blood or serum of the subject.
- the steady-state concentration can be determined by measurement according to techniques available to those of skill or can be based on the physical characteristics of the subject such as height, weight and age.
- administration of the same composition may be repeated and the administrations may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.
- administration of the same prophylactic or therapeutic agent may be repeated and the administration may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.
- the antibodies of the invention are administered to a mammal, generally a human, in a pharmaceutically acceptable dosage form such as those known in the art and those discussed above.
- the antibodies of the invention may be administered to a human intravenously as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intra-cerebrospinal, subcutaneous, intra-articular, intrasynovial, intrathecal, or intratumoral routes.
- the antibodies also are suitably administered by peritumoral, intralesional, or perilesional routes, to exert local as well as systemic therapeutic effects.
- the intraperitoneal route may be particularly useful, for example, in the treatment of ovarian tumors.
- the antibodies provided herein may be useful for the treatment of any disease or condition involving HLA-G, such as cancer, autoimmune disease, and infection.
- any suitable cancer may be treated with the antibodies provided herein.
- suitable cancers include, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor, bile duct cancer, bladder cancer, bone cancer, breast cancer, bronchial tumor, Burkitt Lymphoma, carcinoma of unknown primary origin, cardiac tumor, cervical cancer, chordoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myeloproliferative neoplasm, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, ductal carcinoma, embryonal tumor, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma, fibrous histiocytoma, Ewing sar
- any suitable autoimmune disease may be treated with the antibodies provided herein.
- suitable autoimmune diseases, or diseases with an autoimmune component include, for example, acute disseminated encephalomyelitis (ADEM), acute necrotizing hemorrhagic leukoencephalitis, Addison's disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM/anti-TBM nephritis, antiphospholipid syndrome (APS), autoimmune angioedema, autoimmune aplastic anemia, autoimmune dysautonomia, autoimmune hepatitis, autoimmune hyperlipidemia, autoimmune immunodeficiency, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune thrombocytopenic purpura (ATP), autoimmune thyroid disease, autoimmune urticarial, axonal &
- any suitable infection may be treated with the antibodies provided herein.
- suitable infections include, for example, hepatitis A virus, hepatitis B virus, hepatitis C virus (HCV), human immunodeficiency virus (HIV), and other viral infections.
- Some embodiments provide for treatment of a subject suffering from cancer, a chronic infection, or from an inflammatory disease, comprising the step of administering to the subject a pharmaceutical composition comprising an effective amount of any of the antibodies set forth herein. Some embodiments provide for treatment of a subject suffering from cancer, a chronic infection, or from an inflammatory disease, comprising the step of administering to the subject a pharmaceutical composition comprising an effective amount of any of the antibodies set forth herein in combination with an effective amount of another antibody set forth herein.
- the cancer is a hematological cancer.
- Some embodiments provide a method for modulating immune system function in a subject in need thereof, comprising the step of contacting a population of immune cells of the subject with a pharmaceutical composition comprising an effective amount of the antibody as set forth herein, under conditions such that the immune system is modulated. Some embodiments provide a method for modulating immune system function in a subject in need thereof, comprising the step of contacting a population of immune cells of the subject with an effective amount of any of the antibodies set forth herein in combination with an effective amount of another antibody set forth herein.
- the antibody comprises a bispecific antibody or a complexing antibody.
- the bispecific antibody or the complexing antibody is administered in an amount sufficient to achieve 1, 2, 3, 4, 5, 6, 7, or 8 of the following in the subject:
- the method for modulating immune system function in a subject in need thereof further comprises administering chemotherapy, administering radiation therapy, and/or administering one or more additional therapeutic agents.
- the one or more additional therapeutic agents comprise one or more immunostimulatory agents.
- the one or more immunostimulatory agents comprise an antagonist to an inhibitory receptor of an immune cell.
- the inhibitory receptor is at least one of ILT2, ILT3, ILT4, KIR2DL4, CTLA-4, PD-1, CD39, CD73, PD-L1, PD-L2, LAG-3, TIGIT, B7-H3, B7-H4, Tim3, neuritin, BTLA, CECAM-1, CECAM-5, VISTA, LAIR1, CD160, 2B4, TGF-B, NKG2A, and/or a Killer-cell immunoglobulin-like receptor (KIR).
- the one or more immunostimulatory agents comprise an agonist of a co-stimulatory receptor of an immune cell.
- the co-stimulatory receptor comprises one or more of OX40, CD2, CD27, ICAM-1, LFA-1, ICOS (CD278), 4-1BB (CD137), GITR, CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp30, NKp46, NKp80, CD160, and/or a CD83 ligand.
- the one or more immunostimulatory agents comprise a cytokine.
- the cytokine is at least one of IL-1, IL-2, IL-5, IL-7, IL-10, IL-12, IL-15, IL-21, and/or IL-27.
- the one or more immunostimulatory agents comprise an oncolytic virus.
- the oncolytic virus comprises one or more of the oncolytic virus is a Herpes simplex virus, a Vesicular stomatitis virus, an adenovirus, a Newcastle disease virus, a vaccinia virus, or a maraba virus.
- the one or more immunostimulatory agents comprise a chimeric antigen engineered T cell. In some embodiments, immunostimulatory agents comprise a bi- or multi-specific T cell directed antibody. In some embodiments, the one or more immunostimulatory agents comprises or consists of an ADCC competent antibody that may target CD19, CD20, EGFR, Her2, SLAMF7, CD52, BCMA, GD2, CD38, or CCR4. In some embodiments, the ADCC competent antibody is effector enhanced through afucosylation, point mutations, or otherwise.
- the one or more immunostimulatory agents comprise a bi-specific T cell engager and/or CAR-T therapy, CAR-NK therapy, CAR-macrophage therapy, adoptive T cell therapy.
- the antibodies provided herein are used in diagnostic applications and/or diagnostic methods.
- an anti-HLA-G antibody may be useful in assays for HLA-G protein.
- the antibody can be used to detect the expression of HLA-G in various cells and tissues.
- the antibody can be used to detect the soluble HLA-G in fluids.
- the fluids comprise or consist of blood, serum, ascites, and/or other fluids.
- the assays may be useful, for example, evaluating cancer and autoimmune disease.
- the diagnostic method comprises or consists of detecting tumor expressed HLA-G. In some embodiments, the diagnostic method comprises or consists of detecting soluble HLA-G. In some embodiments the detection method comprises or consists of detecting HLA-G expression on immune cells.
- the antibody may be labeled with a detectable moiety. Suitable detectable moieties include, but are not limited to radioisotopes, fluorescent labels, and enzyme-substrate labels.
- the anti-HLA-G antibody need not be labeled, and the presence thereof can be detected using a labeled antibody which specifically binds to the anti-HLA-G antibody.
- the antibodies of the invention may be used as affinity purification agents.
- the antibodies may be immobilized on a solid phase such a resin or filter paper, using methods well known in the art.
- the immobilized antibody is contacted with a sample containing the HLA-G protein (or fragment thereof) to be purified, and thereafter the support is washed with a suitable solvent that will remove substantially all the material in the sample except the HLA-G protein, which is bound to the immobilized antibody. Finally, the support is washed with another suitable solvent, such as glycine buffer, pH 5.0, that will release the HLA-G protein from the antibody.
- an anti-HLA-G antibody provided herein is provided in the form of a kit, i.e., a packaged combination of reagents in predetermined amounts with instructions for performing a procedure.
- the procedure is a diagnostic assay. In other embodiments, the procedure is a therapeutic procedure.
- the kit further comprises a solvent for the reconstitution of the anti-HLA-G antibody.
- the anti-HLA-G antibody is provided in the form of a pharmaceutical composition.
- HLA-G antibodies were selected from a synthetic library of human antibodies presented on the surface of yeast cells in IgG format, as generally described, e.g., in WO2009036379; WO2010105256; WO2012009568; and Xu et al., Protein Eng. Des. Sel., 2013, 26:663-670 (each incorporated by reference in its entirety), and more specifically as provided below.
- the sequences and characteristics of the antibodies isolated from the recombinant library are provided in Table S.
- the antigen was biotinylated human HLA-G, decreasing concentrations of antigen were used in each subsequent round of selection.
- some rounds of selection were employed to reduce the number of non-specific binders utilizing soluble membrane proteins from CHO cells (see WO2014179363 and Xu et al., Protein Eng. Des. Sel., 2013, 26:663-670, each incorporated by reference in its entirety).
- deselections against recombinant HLA-A/B/C proteins were performed to maintain specific binding to HLA-G. After the final round of sorting, yeast were plated and individual colonies were picked for characterization and for nomination of clones for affinity maturation.
- Antibody variable domains of interest were synthesized, with codon optimization to maximize transient expression in host cells. The variable regions were cloned into expression vectors containing human immunoglobulin constant domains and their sequence confirmed. Antibody heavy and light chain vector pairings were transfected into Expi293 cells using the Expifectamine system (Invitrogen). Transient cultures were harvested on day 4 and clarified cell culture supernatant IgG titer was estimated using Bio-Layer Interferometry (BLI) using Octet (ForteBio) alongside standards. Antibodies were subsequently purified on a Protein A column and eluted using low pH glycine. Purified antibody samples were then buffer-exchanged or dialyzed into downstream assay-compatible buffers.
- Antibody purity was assessed by running samples on SDS-PAGE and on an analytical size exclusion chromatography column.
- Light Chain Shuffling Heavy chain plasmids were extracted from na ⁇ ve outputs (described herein) and transformed into a pre-made na ⁇ ve light chain library with a diversity of 10E+06. Selections were performed as described above with one round of MACS sorting and three rounds of FACS sorting using decreasing amounts of biotinylated HLA-G antigen for respective rounds.
- CDR-H1 and CDR-H2 Selection The CDR-H3s from clones selected from light chain batch diversification, light chain diversification, and naive discovery efforts were independently recombined into premade libraries with CDR-H1 and CDR-H2 variants of a diversity of >10E+8. Selections were performed using HLA-G antigen. Affinity pressures were applied by using decreasing concentrations of antigen and HLA-G specificity was maintained with deselections against HLA-A/B/C antigens.
- CDR-H3 Selection After characterization of CDR-H1 and CDR-H2 variants, clones with binding to HLA antigens outside of HLA-G were removed. Chemical liabilities were also removed from the variable regions when applicable. The remaining clones obtained from the CDR-H1 and CDR-H2 selection procedure were subject to additional rounds of affinity maturation via walking dimer mutagenesis of the CDR-H3. Selections were performed using HLA-G as antigen generally as described above, except for employing FACS sorting for all selection rounds.
- CDR-L1, L2, L3 Selection Clones obtained from the CDR-H1 and CDR-H2 selection procedure were subject to additional rounds of affinity maturation via mutagenesis of the light chain.
- the CDR-L1 and CDR-L2 diversity was derived from a pre-made library while CDR-L3 diversity was derived from walking monomer mutagenesis. Selections were performed using HLA-G as antigen, starting with one round of MACS followed by three rounds of FACS in the CDR-L1, L2, L3 process described here.
- Binding kinetics were measured using the Octet Red96 system (Pall ForteBio) at 30° C. in running buffer (1 ⁇ Pall ForteBio Kinetics Buffer diluted into 1 ⁇ PBS pH 7.4).
- 0.16 ⁇ g % ml of biotinylated recombinant HLA-G/ ⁇ 2m/peptide heterotrimer was loaded onto streptavidin (SA) biosensors to a binding response of approximately 0.25 nm.
- SA streptavidin
- the avid K D values ranged from 11.7 nanomolar to sub picomolar with off-rates (k off ) ranging from 0.007 sec ⁇ 1 to the Octet off-rate limit (1.0 ⁇ 10-7 sec ⁇ 1 ).
- Monovalent K D values ranged from 0.187 nM to 208 nM, but monovalent affinities for clones that had weaker avid affinities were not determined.
- Epitope binning assays to recombinant HLA-G heterotrimer were determined using the Octet Red96 system (Pall ForteBio) at 30′C in running buffer (1 ⁇ Pall ForteBio Kinetics Buffer diluted into 1 ⁇ PBS pH 7.4). Briefly, 0.16 ⁇ g/ml of biotinylated recombinant HLA-G/ ⁇ 2m/peptide heterotrimer was loaded onto streptavidin (SA) biosensors to a binding response of approximately 0.25 nm. After a short baseline step in running buffer, the biosensor was dipped into 20 ⁇ g/ml of each mAb and continued until the binding response to HLA-G reached saturation. For the competing association step, equimolar concentrations of each mAb to the saturating mAb was used.
- SA streptavidin
- Epitope binning was performed in each direction (every mAb was used as both the saturating mAb (association step 1) as well as the competing mAb (association step 2)). Self-blocking sensorgrams are shown in gray. Non-self sensograms are shown in black; black sensorgrams represent the pairwise binning mAb. Sensorgrams from only the second association step were shown in FIG. 2 .
- FIG. 2A provides biolayer interferometry sensorgrams showing tested antibodies that bind HLA-G can be divided into three distinct chemical bins, with one chemical bin being further divided.
- Gray sensorgrams indicate self-blocking; black sensorgrams indicate pairwise binning.
- the y-axis show saturating antibody; the x-axis shows competing antibody.
- FIG. 2B provides biolayer sensorgrams showing antibodies (Fabs) that bind HLA-G and can be separated into two sub-bins from a broader bin 1.
- Bin 1a Fabs do not block competing bin 1b Fabs.
- bin 1b Fabs block bin 1a Fabs.
- gray sensorograms indicated self-blocking and black sensorograms represent pairwise binning.
- the y-axis represents the saturating Fab and the x-axis represents the competing Fab.
- Example 5 Anti-HLA-G Antibodies that Block HLA-G Interaction/Binding to Recombinant ILT2 and ILT4
- Blocking assays between recombinant HLA-G heterotrimer and recombinant extracellular domain of ILT2 or ILT4 proteins was determined using the Octet Red96 system (Pall ForteBio) at 30° C. in running buffer (1 ⁇ Pall ForteBio Kinetics Buffer diluted into 1 ⁇ PBS pH 7.4). Briefly, 0.16 ⁇ g/ml of biotinylated recombinant HLA-G/2m/peptide heterotrimer was loaded onto streptavidin (SA) biosensors to a binding response of approximately 0.25 nm.
- SA streptavidin
- the biosensor was dipped into at least 200 nM of each mAb (up to 0.5 ⁇ M for weakly binding mAbs) and continued until the binding response to HLA-G reached saturation.
- a second association step immediately followed by dipping into wells containing dimerized ILT2 or ILT4. Dimers were obtained via pre-incubation of the His-tagged ILT2 or ILT4 with anti-His mAb (MAB050, R&D Systems).
- ILT2/ILT4 binding response to mAb-saturated HLA-G black sensorgrams
- Sensorgrams from the second association step are shown in FIG. 3 .
- the provided sensorgrams show antibodies that bind and fully block HLA-G interaction with ILT2 and ILT4, for example, the bin1a and bin1b antibodies 38381 and 38358, respectively.
- gray sensorgrams indicate ILT2 or ILT4 binding in the absence of antibody; black sensorgrams represent ILT2 or ILT4 binding in the presence of antibody.
- FIG. 3 also provides biolayer interferometry sensorgrams showing antibodies that bind but do not block HLA-G interaction with ILT2 or ILT4, for example, the bin 3 antibodies such as 33357.
- Gray sensorgrams indicate ILT2 or ILT4 binding response in the absence of antibody; black sensorgrams indicate ILT2 or ILT4 binding in the presence of antibody.
- the provided sensorgrams also show antibodies that bind and block HLA-G interaction with ILT2 or ILT4 to an intermediate effect, such as the bin 2 antibody 38389.
- JEG-3 parentals or HLA-G-knock out (JEG-3 KO) cells were incubated with 100 nM of anti-HLA-G antibodies for 2 hours at 4° C. in wash buffer (Phosphate Buffered Saline (PBS), 2% Fetal bovine serum (FBS) and 2 mM EDTA). Cells were then washed in wash buffer and incubated with an APC conjugated secondary antibody (goat anti-human IgG Kappa) at a 1:500 dilution in wash buffer for 30 minutes at 4° C.
- wash buffer Phosphate Buffered Saline (PBS), 2% Fetal bovine serum (FBS) and 2 mM EDTA.
- the results are shown in FIG. 4 .
- the shaded histogram represents binding of an isotype control to JEG-3 cells at the same concentration.
- Example 7 Anti-HLA-G Antibodies Abrogate Suppression Mediated Through HLA-G-ILT2 or ILT4 Interaction in NKL Killing Assay
- NKL (Effector) cells were co-incubated with 721.221 (Target) cells+/ ⁇ HLA-G expression at an E:T ratio of 4:1 overnight at 37° C.
- 721.221s were pre-incubated with 200 nanomolar (nM) Fab fragments or full-length intact anti-HLA-G antibodies for 60 minutes at 37° C.
- nM nanomolar
- 721.221 cells were labelled with 1:1000 CellTrace Violet (CTV) (Invitrogen) in 37° C. PBS.
- CTV CellTrace Violet
- Antibody MEM-G/9 is a commercially available antibody (See, Fournel et al., Tissue Antigens 200: 55: 510-518 (1999), which is incorporated by reference in its entirety herein, including any drawings).
- FIG. 5A (Fab fragments) and FIG. 5B (intact IgG) show the effect on NKL cells that endogenously express ILT2.
- the percent of dead target cells is shown for each antibody (indicated as a unique clone number in the figure) in addition to control values representing minimum and maximum killing in the presence and absence of HLA-G, respectively.
- Bin 1 antibodies show the best blockade of all the antibodies tested.
- FIG. 5C demonstrates the dose response of a specific Bin 1 anti-HLA-G Fab fragment for blockade of HLA-G-mediated suppression of NKL killing through endogenously expressed ILT2.
- FIG. 5D demonstrates the dose response of a specific Bin 1 anti-HLA-G Fab fragment for blockade of HLA-G-mediated suppression of NKL killing through engineered expression of ILT4 (engineered cell line modified by knocking down ILT2 and retrovirally transduced to express ILT4).
- Example 8 Fab Fragments of Anti-HLA-G Antibodies Reverse HLA-G Mediated Suppression of Macrophage Phagocytosis, NK Cell Cytotoxicity, and CD8 + T Cell Activity
- CD14 + enriched cells were differentiated into adherent macrophages by incubating at 37° C., 5% CO 2 for 7 days in complete RPMI (cRPMI) with recombinant human M-CSF. Cells were harvested after 7 days, washed, and resuspended in cRPMI. Cells were plated in a 96-well round bottom plate at 50,000 cells/well in 50 ⁇ l cRPMI and incubated at 37° C., 5% CO 2 , before being combined with the target cells.
- cRPMI complete RPMI
- the target cells consisting of either 721.221 parental cells or 721.221-HLA-G, were stained with CTV (1:1000) at 37° C. in PBS, washed and plated in cRPMI at 25,000 cells per well. Cells were subsequently incubated with anti-CD47 antibody with or without anti-HLA-G Fabs for 1 hour at 37° C., 5% CO 2 . The mixture of 721.221 and antibody was then combined with macrophages and incubated for either 2 hours or overnight at 37° C., 5% CO 2 . The final ratio of macrophage to 721.221 target cell was 2:1.
- macrophages were assayed for the presence of CTV as a readout of phagocytic uptake of CTV + target cells. Live cells were gated on CD11b + /CTV + and reported as a percent of total live macrophages. For the overnight assay, macrophage killing activity was assessed by measuring absolute counts of remaining live CTV + cells per well.
- FIG. 6A compares results between the two hour and overnight assay formats using an anti-HLA-G antibody (Fab fragment).
- the overnight assay achieves similar results as the two hour assay that directly measures phagocytosis of target cells.
- FIG. 6B shows the results of Fab fragments of each anti-HLA-G antibody that were tested in the overnight assay to determine the level of restored phagocytic activity.
- HLA-G expressing target cells 721.221-HLA-G
- Fab fragment Bin 1 antibody
- human primary NK cells Prior to antibody pre-treatment, 721.221 cells were labelled with 1:1000 CellTrace Violet (CTV) (Invitrogen) in 37° C. PBS.
- CTV CellTrace Violet
- the results are shown in FIG. 6C .
- the percent of dead target cells is shown for the Bin 1 antibody (Fab) in addition to control values representing co-cultures with 721.221 target cells with and without HLA-G expression (noted as HLA-G and no HLA-G in figure, respectively).
- An isotype control Fab (Ctrl Fab) was used as a negative control.
- FCS data was analyzed using FlowJo version 10 analysis software (FlowJo, LLC). Gates were made to select single cells, live cells, and the cell type of interest.
- CD8 + T cell populations were defined based on CD8 + ILT2 + or CD8 + ILT2 ⁇ . To determine the percent of cells positive for CD107a, IFN- ⁇ , or TNF- ⁇ , gating was performed on each CD8 + T cell population and determined using fluorescence minus one cells and unstimulated cells.
- results depicted in FIG. 6D demonstrate that blockade of HLA-G with an anti-HLA-G antibody (representative Bin 1 clone) restored CD107a, IFN- ⁇ , and TNF- ⁇ expression in CD8 + ILT2 + T cells in a dose-dependent manner. There was no effect from HLA-G target cell expression or anti-HLA-G antibody treatment on CD8 + ILT2 ⁇ cells (data not shown).
- Binding of antibodies to HLA antigens was determined using the LABScreen single antigen class I-combi assay (One Lambda). Antibodies at concentrations greater than 300 nM were incubated with single antigen LABScreen beads in binding buffer (Phosphate Buffered Saline, 10% FBS, 2 mM EDTA) for 45 minutes in the dark at room temperature with gentle shaking. Beads were washed twice with 200 ⁇ L of IX LABScreen wash buffer in a 96-well V-bottom plate by centrifugation at 1500 g and removal of buffer by aspiration.
- binding buffer Phosphate Buffered Saline, 10% FBS, 2 mM EDTA
- Antibody 87G is a commercially available antibody and represents a blocking antibody (See, Odum et al., Eur. J. Immunol. 22: 2121-2131 (1991) and Lee et al., Immunity, 591-600 Volume 3, Issue 5 (1995), each of which is incorporated by reference in its entirety herein, including any drawings).
- Binding of antibodies to physiological levels of native HLA class Ia proteins was assessed by flow cytometry on a collection of twenty-eight B-LCL cell lines (shown in Table X). Cells were obtained from the International Histocompatibility Working Group cell line collection that holds a repository of B-LCL cell lines which have been HLA-typed. The cells were maintained in supplemented RPMI-1640 media containing 15% fetal bovine serum.
- anti-HLA antibodies were first conjugated to DyLight 650 (Thermo Fisher) by primary amine labeling via the NHS-ester moiety. Unconjugated dye was removed by flowing the antibody preparation through dye removal resin. Conjugation efficiency was between 1 to 3 moles of DyLight 650 per mole of antibody.
- B-LCL cell lines (ranging from 10,000 to 100,000 cells per well) were incubated with 300 nM of labeled antibodies in cold PBS containing 10% FBS and human Fc block (BD Biosciences). After 2 hours at 4° C., cells were washed twice in cold wash buffer (Phosphate Buffered Saline, 2% FBS, 2 mM EDTA) followed by sample acquisition on a BD FACS Celesta instrument.
- HLA class I expression To assess overall HLA class I expression, a pan HLA class I antibody, clone W6/32, conjugated to FITC was incubated separately with each individual cell line. All cell lines were strongly positive for class I expression (data not shown). Data was exported as FCS files and analyzed using FlowJo software v10. Gating was performed on live singlet cells using DAPI for live-dead discrimination. Geometric MFI is shown for each B-LCL cell line.
- Binding levels are provided as geometric MFI. Class I-negative 721.221 cell lines with and without expression of HLA-G were used as controls.
- 721.221 LCL cells (expressing various point mutants or a domain swap where the primary amino acid sequence encoding the alpha 3 domain was substituted with the analogous sequence from HLA-A*101) were incubated with each antibody (100 nM) in wash buffer (Phosphate Buffered Saline, 2% FBS, 2 mM EDTA) for 60 minutes at 4° C. Cells were then washed with cold wash buffer and incubated with fluorescently labelled secondary antibody at 4° C. for 30 minutes. Numbered antibodies were incubated with 1:500 R-Phycoerythrin labelled goat-anti-human IgG (Jackson ImmunoResearch).
- FIG. 9A shows the evaluation of HLA-G antibodies binding to various forms of HLA-G after site directed mutagenesis.
- FIG. 9B provides representative antibody binding histograms for each of the three point mutants (F195S, Y197A, Y197H, E198A).
- NOD/SCID mice were implanted subcutaneously with 10 million HLA-G expressing 721.221 cells in Matrigel on the right flank.
- mice were randomized into groups based on tumor volume and dosed intraperitoneally with 300 ⁇ g of either an effector competent anti-HLA-G human IgG1 antibody (hIgG1 WT), the same anti-HLA-G antibody with mutations in the Fe domain to abrogate Fc receptor interactions (hIgG1_AAA), or left untreated.
- a second dose of antibody was given three days later.
- Data provided in FIG. 10 represents the percent change in tumor volume six days after initial treatment.
- Table S provides sequences referred to herein.
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Abstract
Description
| TABLE 1 |
| Residues in CDRs according to Kabat |
| and Chothia numbering schemes. |
| CDR | Kabat | Chothia | ||
| L1 | L24-L34 | L24-L34 | ||
| L2 | L50-L56 | L50-L56 | ||
| L3 | L89-L97 | L89-L97 | ||
| H1 (Kabat Numbering) | H31-H35B | H26-H32 or H34* | ||
| H1 (Chothia Numbering) | H31-H35 | H26-H32 | ||
| H2 | H50-H65 | H52-H56 | ||
| H3 | H95-H102 | H95-H102 | ||
| *The C-terminus of CDR-H1, when numbered using the Kabat numbering convention, varies between H32 and H34, depending on the length of the CDR. | ||||
| Acidic Residues | D and E | ||
| Basic Residues | K, R, and H | ||
| Hydrophilic Uncharged Residues | S, T, N, and Q | ||
| Aliphatic Uncharged Residues | G, A, V, L, and I | ||
| Non-polar Uncharged Residues | C, M, and P | ||
| Aromatic Residues | F, Y, and W | ||
| Alcohol Group-Containing | S and T |
| Residues | |
| Aliphatic Residues | I, L, V, and M |
| Cycloalkenyl-associated Residues | F, H, W, and Y |
| Hydrophobic Residues | A, C, F, G, H, I, L, M, V, W, and Y |
| Negatively Charged Residues | D and E |
| Polar Residues | C, D, E, H, K, N, Q, R, S, and T |
| Positively Charged Residues | H, K, and R |
| Small Residues | A, C, D, G, N, P, S, T, and V |
| Very Small Residues | A, G, and S |
| Residues Involved in Turn | A, C, D, E, G, H, K, N, Q, R, S, |
| Formation | P and T |
| Flexible Residues | Q, T, K, S, G, P, D, E, and R |
| Group 1 | A, S, and T | ||
| Group 2 | D and E | ||
| Group 3 | N and Q | ||
| Group 4 | R and K | ||
| Group 5 | I, L, and M | ||
| Group 6 | F, Y, and W | ||
| Group A | A and G | ||
| Group B | D and E | ||
| Group C | N and Q | ||
| Group D | R, K, and H | ||
| Group E | I, L, M, V | ||
| Group F | F, Y, and W | ||
| Group G | S and T | ||
| Group H | C and M | ||
Additional conservative substitutions may be found, for example, in Creighton, Proteins: Structures and Molecular Properties 2nd ed. (1993) W. H. Freeman & Co., New York, N.Y. An antibody generated by making one or more conservative substitutions of amino acid residues in a parent antibody is referred to as a “conservatively modified variant.”
-
- a) inhibition of immune suppression;
- b) reduction of levels of regulatory T cells;
- c) increase an activity of myeloid cells;
- d) increase in activity of cytotoxic T lymphocytes, NK cells, B cells, neutrophils, monocytes, macrophages, and/or dendritic cells;
- e) increase in phagocytic activity;
- f) inhibition of metastasis;
- g) inhibition of tumor growth; and/or
- h) induction of tumor regression.
In some embodiments, the bispecific antibody binds HLA-G and HLA-E.
| TABLE X | |||||||
| Ethnic/Population | Workshop | ||||||
| IHW ID | Alternate ID | Sex | Group | Involvement | HLA A* | HLA B* | HLA Cw* |
| IHW09367 | LCK | Asian | 13 | 0203 | 1102 | 4601 | 380201 | 0702 | 1202 | |
| IHW09458 | FH70EY | M | 13 | 3002 | 6802 | 0801 | 5301 | 0401 | 07 | |
| IHW09383 | FH9 | M | Other | 13 | 2402 | 3303 | 4801 | 44032 | 0801 | 0701 |
| IHW09397 | DUG150 | Unknown | 13 | 02 | 680101 | 5802 | 4501 | 0602 | 1601 | |
| IHW09057 | TEM | M | Jewish | 10, 12 | 6601 | 3801 | 1203 | |||
| IHW09010 | AMAI | M | Algerian | 10, 12 | 6802 | 5301 | 0401 | |||
| IHW09436 | FH48 | M | Caucasian | 13 | 2402 | 0201 | 4427 | 070201 | 070201 | 0704 |
| IHW01167 | 1413-1090 | M | Caucasian | CEPH | 680102 | 0201 | 0801 | 4402 | 0701 | 0501 |
| IHW01075 | 1344-8354 | F | Caucasian | CEPH | 2402 | 0301 | 4001 | 5101 | 030401 | 0102 |
| IHW01185 | 1416-1337 | M | Caucasian | CEPH | 0205 | 2501 | 4901 | 4402 | 0701 | 0501 |
| IHW09431 | FH43 | M | American Black | 13 | 3001 | 3301 | 5301 | 8101 | 04 | 08 |
| IHW01124 | 1362-8563 | M | Caucasian | CEPH | 0201 | 2902 | 3501 | 4403 | 0401 | 1601 |
| IHW01133 | 1362-8572 | F | Caucasian | CEPH | 2902 | 2601 | 4403 | 4402 | 1601 | 0501 |
| IHW01092 | 1346-8603 | M | Caucasian | CEPH | 0201 | 1101 | 0702 | 3501 | 0702 | 0401 |
| IHW09371 | ISH4 | Asian | 13 | 0218 | 1101 | 1501 | 4601 | 0102 | 040101 | |
| IHW09433 | FH45 | M | Asian | 13 | 1101 | 02 | 3802 | 4101 | 0702 | 17 |
| IHW09380 | FH6 | M | Hispanic | 13 | 2402 | 2901 | 2702 | 0705 | 1505 | 020202 |
| IHW09411 | FH29 | F | Hispanic | 13 | 0201 | 2902 | 1516 | 440301 | 1402 | 1601 |
| IHW09401 | TER-259 | USA White/ | 13 | 3201 | 6802 | 0801 | 44020101 | 0102 | 07 | |
| American Indian | ||||||||||
| IHW09398 | FH18 | F | American Black | 13 | 3601 | 7401 | 5301 | 5703 | 0401 | 0701 |
| IHW09382 | FH8 | F | Am. Black | 13 | 110101 | 3402 | 8201 | 270502 | 0302 | 0102 |
| IHW01026 | 1332-8257 | F | Caucasian | CEPH | 0301 | 3001 | 3501 | 0702 | 0401 | 0702 |
| IHW09409 | FH27 | M | Native American | 13 | 310102 | 3401 | 350101 | 380201 | 0401 | 0702 |
| IHW09452 | FH64 | Unknown | 13 | 02 | 3201 | 44 | 1801 | 05 | 07 | |
| IHW01028 | 1332-8259 | F | Caucasian | CEPH | 0301 | 0301 | 3501 | 2705 | 0401 | 020202 |
| IHW01061 | 1341-8465 | F | Caucasian | CEPH | 0201 | 680102 | 0702 | 0702 | 0702 | 0702 |
| IHW01099 | 1347-8434 | M | Caucasian | CEPH | 2501 | 0101 | 0801 | 1501 | 0701 | 0602 |
| IHW01136 | 1362-8575 | M | Caucasian | CEPH | 0101 | 1101 | 0702 | 5101 | 0702 | 1502 |
| TABLE S |
| Sequences. |
| SEQ | ||||
| ID | Re- | Scheme/ | ||
| NO: | | Clone | Sequence | |
| 1 | CDR- | Chothia | GGSISSSDY | |
| |
||||
| 2 | CDR- | Chothia | GGSISSSST | |
| |
||||
| 3 | CDR- | Chothia | GGSISSSDT | |
| H1 | ||||
| 4 | CDR- | Chothia | GGSISSADN | |
| |
||||
| 5 | CDR- | Chothia | GGSVSSSST | |
| |
||||
| 6 | CDR- | Chothia | GYSTSSGY | |
| H1 | ||||
| 7 | CDR- | Chothia | GYSILSGY | |
| H1 | ||||
| 8 | CDR- | Chothia | GYSISSGH | |
| |
||||
| 9 | CDR- | Chothia | GYSISSGF | |
| |
||||
| 10 | CDR- | Chothia | GFTFDNY | |
| |
||||
| 11 | CDR- | Chothia | GFTFSDY | |
| |
||||
| 12 | CDR- | Chothia | GFTFSSS | |
| H1 | ||||
| 13 | CDR- | Chothia | GGSISSSN | |
| H1 | ||||
| 14 | CDR- | Chothia | GGSISSSSY | |
| H1 | ||||
| 15 | ||||
| 16 | ||||
| 17 | ||||
| 18 | CDR- | Kabat | SSDYYWG | |
| H1 | ||||
| 19 | CDR- | Kabat | SSSTYWA | |
| H1 | ||||
| 20 | CDR- | Kabat | SSSTYWG | |
| H1 | ||||
| 21 | CDR- | Kabat | SSDTYWG | |
| H1 | ||||
| 22 | CDR- | Kabat | SADNYWG | |
| H1 | ||||
| 23 | CDR- | Kabat | SSSTYWS | |
| H1 | ||||
| 24 | CDR- | Kabat | SGYYWG | |
| H1 | ||||
| 25 | CDR- | Kabat | SGYYWF | |
| H1 | ||||
| 26 | CDR- | Kabat | SGHYWI | |
| H1 | ||||
| 27 | CDR- | Kabat | SGFYWT | |
| H1 | ||||
| 28 | CDR- | Kabat | SGYYWL | |
| H1 | ||||
| 29 | CDR- | Kabat | SGHYWT | |
| H1 | ||||
| 30 | CDR- | Kabat | NYAMH | |
| H1 | ||||
| 31 | CDR- | Kabat | DYYMS | |
| H1 | ||||
| 32 | CDR- | Kabat | SSAMA | |
| H1 | ||||
| 33 | CDR- | Kabat | SSNWWS | |
| H1 | ||||
| 34 | CDR- | Kabat | SSSYYWG | |
| H1 | ||||
| 35 | ||||
| 36 | ||||
| 37 | ||||
| 38 | CDR- | Chothia | YYSGS | |
| H2 | ||||
| 39 | CDR- | Chothia | SSSGS | |
| |
||||
| 40 | CDR- | Chothia | HHSGA | |
| H2 | ||||
| 41 | CDR- | Chothia | HYSGS | |
| H2 | ||||
| 42 | CDR- | Chothia | AYSGS | |
| H2 | ||||
| 43 | CDR- | Chothia | SYNAL | |
| H2 | ||||
| 44 | CDR- | Chothia | YHSGS | |
| H2 | ||||
| 45 | CDR- | Chothia | YHSAS | |
| H2 | ||||
| 46 | CDR- | Chothia | SARAGI | |
| H2 | ||||
| 47 | CDR- | Chothia | ASSGSV | |
| H2 | ||||
| 48 | CDR- | Chothia | SGSGIT | |
| H2 | ||||
| 49 | CDR- | Chothia | SYSGS | |
| |
||||
| 50 | CDR- | Chothia | SSSGST | |
| H2 | ||||
| 51 | ||||
| 52 | ||||
| 53 | ||||
| 54 | CDR- | Kabat | SIYYSGSTYYNPSLKS | |
| H2 | ||||
| 55 | CDR- | Kabat | SISSSGSTYYNPSLKS | |
| H2 | ||||
| 56 | CDR- | Kabat | SIHHSGATYYNPSLKS | |
| H2 | ||||
| 57 | CDR- | Kabat | SIHYSGSTLYNPSLKS | |
| H2 | ||||
| 58 | CDR- | Kabat | SIHYSGSTYYNPSLKS | |
| H2 | ||||
| 59 | CDR- | Kabat | GIAYSGSTYYNPSLKS | |
| |
||||
| 60 | CDR- | Kabat | SISYNALTYYNPSLKS | |
| H2 | ||||
| 61 | CDR- | Kabat | SIYHSGSTYYNPSLKS | |
| H2 | ||||
| 62 | CDR- | Kabat | GIYHSASTAYMPSLKS | |
| |
||||
| 63 | CDR- | Kabat | GIYHSGSTYYNPSLKS | |
| H2 | ||||
| 64 | CDR- | Kabat | AIYHSGSTVYNPSLKS | |
| H2 | ||||
| 65 | CDR- | Kabat | GIYHSGSTAYNPSLKS | |
| H2 | ||||
| 66 | CDR- | Kabat | AISARAGITYYADSVKG | |
| H2 | ||||
| 67 | CDR- | Kabat | YIASSGSVIYYADSVKG | |
| H2 | ||||
| 68 | CDR- | Kabat | TISGSGITTWYADSVKG | |
| H2 | ||||
| 69 | CDR- | Kabat | EIYHSGSTNYNPSLKS | |
| H2 | ||||
| 70 | CDR- | Kabat | SISYSGSTYYNPSLKS | |
| H2 | ||||
| 71 | CDR- | Kabat | YISSSGSTIYYADSVKG | |
| H2 | ||||
| 72 | ||||
| 73 | ||||
| 74 | ||||
| 75 | ||||
| 76 | CDR- | GVRRAVPFDY | ||
| H3 | ||||
| 77 | CDR- | GIARAVPFDY | ||
| H3 | ||||
| 78 | CDR- | GPKRAVPFDY | ||
| H3 | ||||
| 79 | CDR- | GVRRAVPFVD | ||
| |
||||
| 80 | CDR- | GVRRAVPFQR | ||
| H3 | ||||
| 81 | CDR- | GTRRAVPFDY | ||
| H3 | ||||
| 82 | CDR- | GVRRAVPFAD | ||
| H3 | ||||
| 83 | CDR- | GIRRAMPFDY | ||
| H3 | ||||
| 84 | CDR- | GQFRAVPFDY | ||
| H3 | ||||
| 85 | CDR- | GGTHTYSRGPMDV | ||
| H3 | ||||
| 86 | CDR- | GGTHTYSRGPFDV | ||
| H3 | ||||
| 87 | CDR- | GGTPIYSRGPLDV | ||
| H3 | ||||
| 88 | CDR- | GGGQTYSRGPLDV | ||
| H3 | ||||
| 89 | CDR- | GGGATYSRGPLDV | ||
| H3 | ||||
| 90 | CDR- | GGTHTYSRGPLDV | ||
| H3 | ||||
| 91 | CDR- | GGTVKYSRGPLDV | ||
| H3 | ||||
| 92 | CDR- | GGQVTYSRGPLDV | ||
| H3 | ||||
| 93 | CDR- | GGEVTYSRGPLDV | ||
| H3 | ||||
| 94 | CDR- | RIGYSYGTAPPFDV | ||
| H3 | ||||
| 95 | CDR- | HGTPRAFDI | ||
| H3 | ||||
| 96 | CDR- | GSRHLNAFNR | ||
| H3 | ||||
| 97 | CDR- | GVYHYDPYGMDV | ||
| H3 | ||||
| 98 | CDR- | TELGKMHFDY | ||
| H3 | ||||
| 99 | CDR- | | ||
| H3 | ||||
| 100 | CDR- | HSSLGTHNWFDP | ||
| |
||||
| 101 | CDR- | EGALSYSWLAAFDI | ||
| |
||||
| 102 | ||||
| 103 | ||||
| 104 | ||||
| 105 | CDR- | RASQSVSSSYLA | ||
| L1 | ||||
| 106 | CDR- | GASQSVSSDYLA | ||
| L1 | ||||
| 107 | CDR- | QASQAVSSNYLA | ||
| L1 | ||||
| 108 | CDR- | GASQSVSSAFLA | ||
| L1 | ||||
| 109 | CDR- | RASQSVSSTYLA | ||
| L1 | ||||
| 110 | CDR- | QASQSVSSSYLA | ||
| L1 | ||||
| 111 | CDR- | KASQAVSSSYLA | ||
| L1 | ||||
| 112 | CDR- | EASQSVSSSYLA | ||
| L1 | ||||
| 113 | CDR- | EASQSVSASYLA | ||
| L1 | ||||
| 114 | CDR- | EASQSVSSAYLA | ||
| L1 | ||||
| 115 | CDR- | RVSQSVSDAYLA | ||
| L1 | ||||
| 116 | CDR- | EVSQSVSASYLA | ||
| L1 | ||||
| 117 | CDR- | RASQSVSSAYLA | ||
| L1 | ||||
| 118 | CDR- | RASNAVSSSYLA | ||
| L1 | ||||
| 119 | CDR- | RASQSINSWLA | ||
| L1 | ||||
| 120 | CDR- | AASQGISSDLA | ||
| L1 | ||||
| 121 | CDR- | RASQDISTYLN | ||
| L1 | ||||
| 122 | CDR- | RSSQSLLHSNGYNYLD | ||
| L1 | ||||
| 123 | CDR- | RASQSISSYLN | ||
| L1 | ||||
| 124 | CDR- | RASQSVSSNLA | ||
| L1 | ||||
| 125 | ||||
| 126 | ||||
| 127 | ||||
| 128 | CDR- | GASSRT | ||
| L2 | ||||
| 129 | CDR- | GAYSLAT | ||
| L2 | ||||
| 130 | CDR- | GASARAT | ||
| L2 | ||||
| 131 | CDR- | GASSREA | ||
| L2 | ||||
| 132 | CDR- | GASNRAA | ||
| L2 | ||||
| 133 | CDR- | GASSRQD | ||
| L2 | ||||
| 134 | CDR- | GASNRAT | ||
| L2 | ||||
| 135 | CDR- | DASSRAS | ||
| L2 | ||||
| 136 | CDR- | DASTRAT | ||
| L2 | ||||
| 137 | CDR- | GASDRAN | ||
| L2 | ||||
| 138 | CDR- | GASYRAT | ||
| L2 | ||||
| 139 | CDR- | DASSLES | ||
| L2 | ||||
| 140 | CDR- | SASSTQS | ||
| L2 | ||||
| 141 | CDR- | DAFNLET | ||
| L2 | ||||
| 142 | CDR- | LGSNRAS | ||
| L2 | ||||
| 143 | CDR- | GASRRAT | ||
| L2 | ||||
| 144 | CDR- | AASSLQS | ||
| L2 | ||||
| 145 | CDR- | GASTRAT | ||
| L2 | ||||
| 146 | ||||
| 147 | ||||
| 148 | ||||
| 149 | CDR- | QQAVHSPYT | ||
| L3 | ||||
| 150 | CDR- | QWAVHSPYT | ||
| L3 | ||||
| 151 | CDR- | QQVVHSPYT | ||
| L3 | ||||
| 152 | CDR- | QQTVHSPYT | ||
| L3 | ||||
| 153 | CDR- | QQAIHSPYT | ||
| L3 | ||||
| 154 | CDR- | QQHSSYPPT | ||
| L3 | ||||
| 155 | CDR- | QQHSLYPPT | ||
| L3 | ||||
| 156 | CDR- | QQFSSYPPT | ||
| L3 | ||||
| 157 | CDR- | QQVSSYPPT | ||
| L3 | ||||
| 158 | CDR- | QQHSIYPPT | ||
| L3 | ||||
| 159 | CDR- | QQYDSHIT | ||
| L3 | ||||
| 160 | CDR- | QQAYLYPIT | ||
| L3 | ||||
| 161 | CDR- | QQLPFLPIT | ||
| L3 | ||||
| 162 | CDR- | MQALGGPWT | ||
| L3 | ||||
| 163 | CDR- | QQYVSDPIT | ||
| L3 | ||||
| 164 | CDR- | QQVGSSPIT | ||
| L3 | ||||
| 165 | CDR- | QQSHLVPRT | ||
| L3 | ||||
| 166 | CDR- | QQANHHPPFT | ||
| L3 | ||||
| 167 | ||||
| 168 | ||||
| 169 | ||||
| 170 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | ||
| YYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSS | ||||
| 171 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | ||
| TYWAWIRQPPGKGLEWIGSISSSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GIARAVPFDYWGQGTLVTVSS | ||||
| 172 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | ||
| TYWGWIRQSPGKGLEWIGSIHHSGATYYNPSLK | ||||
| SRVTISVDTSKNQFSLKTSSVTAADTAVYYCAR | ||||
| GPKRAVPFDYWGQGTLVTVSS | ||||
| 173 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | ||
| TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFVDWGQGTLVTVSS | ||||
| 174 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSAD | ||
| NYWGWIRQPPGKGLEWIGSIHYSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFQRWGQGTLVTVSS | ||||
| 175 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | ||
| TYWGWIRQPPGKGPEWIGSIHYSGSTLYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSS | ||||
| 176 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | ||
| TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSS | ||||
| 177 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | ||
| TYWSWIRQPPGKGLEWIGSISYNALTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GTRRAVPFDTWGQGTLVTVSS | ||||
| 178 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | ||
| TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFADWGQGTLVTVSS | ||||
| 179 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSVSSSS | ||
| TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSS | ||||
| 180 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | ||
| TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GTRRAVPFDYWGQGTLVTVSS | ||||
| 181 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | ||
| TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GIRRAVPFDYWGQGTLVTVSS | ||||
| 182 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | ||
| TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GQFRAVPFDYWGQGTLVTVSS | ||||
| 183 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | ||
| YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPMDVWGQGTTVTVSS | ||||
| 184 | VH | QLQLQESGPRLVKPSETLSLTCAVSGYSISSGY | ||
| YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPFDVWGQGTTVTVSS | ||||
| 185 | VH | LVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | ||
| YWFWIRQPPGKGLEWIGGIYHSASTAYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTPIYSRGPLDVWGQGTTVTVSS | ||||
| 186 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGH | ||
| YWIWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | ||||
| RVTISVDTSKDQFSLKLSSVTAADTAVYYCARG | ||||
| GGQTYSRGPLDVWGQGTTVTVSS | ||||
| 187 | VH | QVQLQESGPGLVKPPETLSLTCAVSGYSISSGH | ||
| YWIWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GGATYSRGPLDVWGQGTTVTVSS | ||||
| 188 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | ||
| YWFWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPLDVWGQGTTVTVSS | ||||
| 189 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGF | ||
| YWTWIRQPPGKGLEWIGAIYHSGSTVYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPLDVWGQGTTVTVSS | ||||
| 190 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | ||
| YWLWIRQPPGKGLEWIGGIYHSASTAYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTVKYSRGPLDVWGQGTTVTVSS | ||||
| 191 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGH | ||
| YWTWIRQPPGKGLEWIGAIYHSGSTVYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GQVTYSRGPLDVWGQGTTVTVSS | ||||
| 192 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | ||
| YWFWIRQPPGKGLEWIGGIYHSGSTAYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GEVTYSRGPLDVWGQGTTVTVSS | ||||
| 193 | VH | EVQLLESGGGLVQPGGSLRLSCAASGFTFDNYA | ||
| MHWVRQAPGKGLEWVSAISARAGITYYADSVKG | ||||
| RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARR | ||||
| IGYSYGTAPPFDVWGQGTTVTVSS | ||||
| 194 | VH | QVQLVESGGGLVQPGGSLRLSCAASGFTFSDYY | ||
| MSWIRQAPGKGLEWVSYIASSGSVIYYADSVKG | ||||
| RFTISRDNAKNSLYLQMNSLRAEDTAVYYCARH | ||||
| GTPRAFDIWGQGTTVTVSS | ||||
| 195 | VH | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSA | ||
| MAWVRQAPGKGLEWVSTISGSGITTWYADSVKG | ||||
| RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKG | ||||
| SRHLNAFNRWGQGTTVTVSS | ||||
| 196 | VH | QVQLQESGPGLVKPSGTLSLTCAVSGGSISSSN | ||
| WWSWVRQPPGKGLEWIGEIYHSGSTNYNPSLKS | ||||
| RVTISVDKSKNQFSLKLSSVTAADTAVYYCARG | ||||
| VYHYDPYGMDVWGQGTTVTVSS | ||||
| 197 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | ||
| YYWGWIRQPPGKGLEWIGSISYSGSTYYNPSLK | ||||
| SRVTISVDTSRNQFSLKLSSVTAADTAVYYCAR | ||||
| TELGKMHFDYWGQGTLVTVSS | ||||
| 198 | VH | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | ||
| YYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLK | ||||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GSPRYMQDWGQGTLVTVSS | ||||
| 199 | VH | QVQLVESGSGLVKPGGSLRLSCAASGFTFSDYY | ||
| MSWIRQAPGKGLEWVSYISSSGSTIYYADSVKG | ||||
| RFTISRDNAKNSLYLQMNSLRAEDTAVYYCARH | ||||
| |
||||
| 200 | VH | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | ||
| YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | ||||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARE | ||||
| GALSYSWLAAFDIWGQGTMVTVSS | ||||
| 201 | ||||
| 202 | ||||
| 203 | ||||
| 204 | VL | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | ||
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAVHSPYTF | ||||
| GGGTKVEIK | ||||
| 205 | VL | EIVLTQSPGTLSLSPGERATLSCGASQSVSSDY | ||
| LAWYQQKPGQAPRLLIYGAYSLATGIPDRFSGS | ||||
| GSGTDFTLTISRLRPEDFAVYYCQWAVHSPYTF | ||||
| GGGTKVEIK | ||||
| 206 | VL | EIVLTQSPGTLSLSPGERATLSCQASQAVSSNY | ||
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVVHSPYTF | ||||
| GGGTKVEIK | ||||
| 207 | VL | EIVLTQSPGTLSLSPGERATLSCGASQSVSSAF | ||
| LAWYQQKPGQAPRLLIYGASARATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVVHSPYTF | ||||
| GGGTKVEIK | ||||
| 208 | VL | EIVLTQSPGTLSLSPGERATLSCRASQSVSSTY | ||
| LAWYQQKPGQAPRLLIYGASSREAGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQTVHSPYTF | ||||
| GGGTKVEIK | ||||
| 209 | VL | EIVLTQSPGTLSLSPGERATLSCQASQAVSSNY | ||
| LAWYQQKPGQAPRLLIYGASNRAAGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAIHSPYTF | ||||
| GGGTKVEIK | ||||
| 210 | VL | EIVLTQSPGTLSLSPGERATLSCQASQSVSSSY | ||
| LAWYQQKPGQAPRLLIYGASNRAAGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVVHSPYTF | ||||
| GGGTKVEIK | ||||
| 211 | VL | EIVLTQSPGTLSLSPGERATLSCKASQAVSSSY | ||
| LAWYQQKPGQAPRLLIYGASSRQDGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVVHSPYTF | ||||
| GGGTKVEIK | ||||
| 212 | VL | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | ||
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSSYPPTF | ||||
| GGGTKVEIK | ||||
| 213 | VL | EIVLTQSPGTLSLSPGERATLSCEASQSVSSSY | ||
| LAWYQQKPGQAPRLLIYGASNRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIK | ||||
| 214 | VL | EIVLTQSPGTLSLSPGFRATLSCEASQSVSASY | ||
| LAWYQQKPGQAPRLLIYDASSRASGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQFSSYPPTF | ||||
| GGGTKVEIK | ||||
| 215 | VL | EIVLTQSPGTLSLSPGERATLSCEASQSVSSAY | ||
| LAWYQQKPGQAPRLLIYDASTRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVSSYPPTF | ||||
| GGGTKVEIK | ||||
| 216 | VL | EIVLTQSPGTLSLSPGERAALSCRVSQSVSDAY | ||
| LAWYQQKPGQAPRLLIYDASSRASGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVSSYPPTF | ||||
| GGGTKVEIK | ||||
| 217 | VL | EIVLTQSPGTLSLSPGERATLSCEVSQSVSASY | ||
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIK | ||||
| 218 | VL | EIVLTQSPGTLSLSPGERATLSCRASQSVSSAY | ||
| LAWYQQKPGQAPRLLIYGASDRANGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIK | ||||
| 219 | VL | EIVLTQSPGTLSLSPGERATLSCRASNAVSSSY | ||
| LAWYQQKPGQAPRLLIYGASDRANGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSIYPPTF | ||||
| GGGTKVEIK | ||||
| 220 | VL | EIVLTQSPGTLSLSPGERATLSCRASNAVSSSY | ||
| LAWYQQKPGQAPRLLIYGASYRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIK | ||||
| 221 | VL | DIQMTQSPSTLSASVGDRVTITCRASQSINSWL | ||
| AWYQQKPGKAPKLLISDASSLESGVPSRFSGSG | ||||
| SGTEFTLTISSLQPDDFATYYCQQYDSHITFGG | ||||
| GTKVEIK | ||||
| 222 | VL | DIQMTQSPSSVSASVGDRVTITCAASQGISSDL | ||
| AWYQQKPGKAPKLLIYSASSTQSGVPSRFSGSG | ||||
| SGTDFTLTISSLQPEDFATYYCQQAYLYPITFG | ||||
| GGTKVEIK | ||||
| 223 | VL | GVQMTQSPSSLSASVGDRVTITCRASQDISTYL | ||
| NWYQQKPGKAPKLLIYDAFNLETGVPSRFSGSG | ||||
| SGTDFTFTISSLQPEDIATYYCQQLPFLPITFG | ||||
| GGTKVEIK | ||||
| 224 | VL | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSN | ||
| GYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDR | ||||
| FSGSGSGTDFTLKISRVEAEDVGVYYCMQALGG | ||||
| PWTFGGGTKVEIK | ||||
| 225 | VL | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | ||
| LAWYQQKPGQAPRLLIYGASRRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQYVSDPITF | ||||
| GGGTKVEIK | ||||
| 226 | VL | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | ||
| LAWYQQKPGQAPRLLIYGASRRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVGSSPITF | ||||
| GGGTKVEIK | ||||
| 227 | VL | DIQMTQSPSSLSASVGDRVTITCRASQSISSYL | ||
| NWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSG | ||||
| SGTDFTLTISSLQPEDFATYYCQQSHLVPRTFG | ||||
| GGTKVEIK | ||||
| 228 | VL | EIVMTQSPATLSVSPGERATLSCRASQSVSSNL | ||
| AWYQQKPGQAPRLLIYGASTRATGIPARFSGSG | ||||
| SGTEFTLTISSLQSEDFAVYYCQQANHHPPFTF | ||||
| GGGTKVEIK | ||||
| 229 | ||||
| 230 | ||||
| 231 | ||||
| 232 | |
33343 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| AAA | YYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GVRRAWPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 233 | IGG1 | 37268 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| AAA | TYWAWIRQPPGKGLEWIGSISSSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GIARAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 234 | IGG1 | 37269 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| AAA | TYWGWIRQSPGKGLEWIGSIHHSGATYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GPKRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 235 | IGG1 | 37271 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| AAA | TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GVRRAVPFVDWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 236 | IGG1 | 37272 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSAD | |
| AAA | NYWGWIRQPPGKGLEWIGSIHYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GVRRAVPFQRWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 237 | IGG1 | 37277 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| AAA | TYWGWIRQPPGKGPEWIGSIHYSGSTLYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GVRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 238 | IGG1 | 38373 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| AAA | TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GVRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 239 | IGG1 | 38375 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| AAA | TYWSWIRQPPGKGLEWIGSISYNALTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GTRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 240 | |
38379 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| AAA | TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GVRRAVPFADWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 241 | |
38381 | QLQLQESGPGLVKPSETLSLTCTVSGGSVSSSS | |
| AAA | TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GVRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 242 | IGG1 | 38383 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| AAA | TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GTRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 243 | |
38386 | QLQLQESCPGLVKPSETLSLTCTVSGGSISSSD | |
| AAA | TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GIRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 244 | IGG1 | 37273 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| AAA | TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GQFRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 245 | |
33361 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | |
| AAA | YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GTHTYSRGPMDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 246 | IGG1 | 35624 | QLQLQESGPRLVKPSETLSLTCAVSGYSISSGY | |
| AAA | YWGWIRQPPCKGLEWIGSIYHSGSTYYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GTHTYSRGPFDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQLWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 247 | |
38410 | LVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | |
| AAA | YWFWIRQPPGKGLEWIGGIYHSASTAYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GTPIYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 248 | |
38418 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGH | |
| AAA | YWIWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | |||
| HC | RVTISVDTSKDQFSLKLSSVTAADTAVYYCARG | |||
| GGQTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 249 | |
38420 | QVQLQESGPGLVKPPETLSLTCAVSGYSISSGH | |
| AAA | YWIWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GGATYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 250 | |
38421 | QVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | |
| AAA | YWFWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GTHTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 251 | |
38422 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGF | |
| AAA | YWTWIRQPPGKGLEWIGAIYHSGSTVYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GTHTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDCWEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 252 | |
38424 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | |
| AAA | YWLWIRQPPGKGLEWIGGIYHSASTAYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GTVKYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 253 | |
38425 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGH | |
| AAA | YWTWIRQPPGKGLEWIGAIYHSGSTVYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GQVTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 254 | |
38426 | QVQLQESGPGIVKPSETLSLTCAVSGYSILSGY | |
| AAA | YWFWIRQPPGKGLEWIGGIYHSGSTAYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | |||
| GEVTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC | ||||
| PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEV | ||||
| TCVVVDVSHFDPEVKFNWYVDGVEVHNAKTKPR | ||||
| EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN | ||||
| KALPAPIEKTISKAKGQPREPQVYTLPPSREEM | ||||
| TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY | ||||
| KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS | ||||
| CSVMHEALHNHYTQKSLSLSPGK | ||||
| 255 | |
37323 | EVQLLESGGGLVQPGGSLRLSCAASGFTFDNYA | |
| AAA | MHWVRQAPGKGLEWVSAISARAGITYYADSVKG | |||
| HC | RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARR | |||
| IGYSYGTAPPFDVWGQGTTVTVSSASTKGPSVF | ||||
| PLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN | ||||
| SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS | ||||
| LGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT | ||||
| CPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPE | ||||
| VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP | ||||
| REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS | ||||
| NKALPAPIEKTISKAKGQPREPQVYTLPPSREE | ||||
| MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN | ||||
| YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF | ||||
| SCSVMHEALHNHYTQKSLSLSPGK | ||||
| 256 | |
38389 | QVQLVESGGGLVQPGGSLRLSCAASGFTFSDYY | |
| AAA | MSWIRQAPGKGLEWVSYIASSGSVIYYADSVKG | |||
| HC | RFTISRDNAKNSLYLQMNSLRAEDTAVYYCARH | |||
| GTPRAFDIWGQGTTVTVSSASTKGPSVFPLAPS | ||||
| SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT | ||||
| SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT | ||||
| YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP | ||||
| APEAAGAPSVFLFPPKPKDTLMISRTPEVTCVV | ||||
| VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY | ||||
| NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP | ||||
| APIEKTISKAKGQPREPQVYTLPPSREEMTKNQ | ||||
| VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP | ||||
| PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM | ||||
| HEALHNHYTQKSLSLSPGK | ||||
| 257 | |
38358 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSA | |
| AAA | MAWVRQAPGKGLEWVSTISGSGITTWYADSVKG | |||
| HC | RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKG | |||
| SRHLNAFNRWGQGTTVTVSSASTKGPSVFPLAP | ||||
| SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL | ||||
| TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ | ||||
| TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC | ||||
| PAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSHEDPENKFNWYVDGVEVHNAKTKPREEQ | ||||
| YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL | ||||
| PAPIEKTISKAKGQPREPQVYTLPPSREEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 258 | |
33303 | QVQLQESHPGLVKPSGTLSLTCAVSGGSISSSN | |
| AAA | WWSWVRQPPGKGLEWIGEIYHSGSTNYNPSLKS | |||
| HC | RVTISVDKSKNQFSLKLSSVTAADTAVYYCARG | |||
| VYHYDPYGMDVWGQGTTVTVSSASTKGPSVFPL | ||||
| APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG | ||||
| ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG | ||||
| TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP | ||||
| PCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVT | ||||
| CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE | ||||
| EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK | ||||
| ALPAPIEKTISKAKGQPREPQVYTLPPSREEMT | ||||
| KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK | ||||
| TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC | ||||
| SVMMEALHNHYTQKSLSLSPGK | ||||
| 259 | |
33342 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| AAA | YYWGWIRQPPGKGLEWIGSISYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| TELGKMHFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP | ||||
| CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE | ||||
| QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA | ||||
| LPAPIEKTISKAKGQPREPQVYTLPPSREEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 260 | |
33299 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| AAA | YYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLK | |||
| HC | SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | |||
| GSPRYMQDWGQGTLVTVSSASTKGPSVFPLAPS | ||||
| SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALT | ||||
| SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT | ||||
| YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP | ||||
| APEAAGAPSVFLFPPKPKDTLMISRTPEVTCVV | ||||
| VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY | ||||
| NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP | ||||
| APIEKTISKAKGQPREPQVYTLPPSREEMTKNQ | ||||
| VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP | ||||
| PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM | ||||
| HEALHNHYTQKSLSLSPGK | ||||
| 261 | |
33351 | QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYY | |
| AAA | MSWIRQAPGKGLEWVSYISSSGSTIYYADSVKG | |||
| HC | RFTISRDNAKNSLYLQMNSLRAEDTAVYYCARH | |||
| SSLGTHNWFDPWGQGTLVTVSSASTKGPSVFPL | ||||
| APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG | ||||
| ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG | ||||
| TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP | ||||
| PCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVT | ||||
| CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE | ||||
| EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK | ||||
| ALPAPIEKTISKAKGQPREPQVYTLPPSREEMT | ||||
| KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK | ||||
| TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC | ||||
| SVMHEALHNHYTQKSLSLSPGK | ||||
| 262 | |
33357 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | |
| AAA | YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | |||
| HC | RVTISVDTSKNQFSLKLSSVTAADTAVYYCARE | |||
| GALSYSWLAAFDIWGQGTMVTVSSASTKGPSVF | ||||
| PLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN | ||||
| SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS | ||||
| LGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT | ||||
| CPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPE | ||||
| VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP | ||||
| REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS | ||||
| NKALPAPIEKTISKAKGQPREPQVYTLPPSREE | ||||
| MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN | ||||
| YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF | ||||
| SCSVMHEALHNHYTQKSLSLSPGK | ||||
| 263 | ||||
| 264 | ||||
| 265 | ||||
| 266 | |
33343 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| HC | YYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 267 | IGG4 | 37268 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| HC | TYWAWIRQPPGKGLEWIGSISSSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GIARAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 268 | IGG4 | 37269 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| HC | TYWGWIRQSPGKGLEWIGSIHHSGATYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GPKRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 269 | IGG4 | 37271 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| HC | TYWGWIRQPPGRGLEWIGSIHYSGSTLYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFVDWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWTVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQRGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 270 | IGG4 | 37272 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSAD | |
| HC | NYWGWIRQPPGKGLEWIGSIHYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFQRWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 271 | IGG4 | 37277 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| HC | TYWGWIRQPPGKGPEWIGSIHYSGSTLYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKOQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 272 | IGG4 | 38373 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| HC | TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 273 | IGG4 | 38375 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| HC | TYWSWIRQPPGKGLEWIGSISYNALTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GTRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 274 | IGG4 | 38379 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| HC | TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFADWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 275 | IGG4 | 38381 | QLQLQESGPGLVKPSETLSLTCTVSGGSVSSSS | |
| HC | TYWSWIRQPPGKGLEWIGGIAYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GVRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVDLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPWCQFNWYVDGVWVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 276 | IGG4 | 38383 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| HC | TYWSWIRQPPGRGLEWIGGIAYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GTRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 277 | IGG4 | 38386 | QLQLQRSGPGLVKPSETLSLTCTVSGGSISSSD | |
| HC | TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GIRRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 278 | IGG4 | 37273 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| HC | TYWGWIRQPPGKGLEWIGSIHYSGSTLYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GQFRAVPFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 279 | IGG4 | 33361 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | |
| HC | YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPMDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 280 | IGG4 | 35624 | QLQLQESGPRLVKPSETLSLTCAVSGYSISSGY | |
| HC | YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPFDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 281 | IGG4 | 38410 | LVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | |
| HC | YWFWIRQPPGKGLEWIGGIYHSASTAYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTPIYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 282 | IGG4 | 38418 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGH | |
| HC | YWIWIRQPPCKGLEWIGGIYHSGSTYYNPSLKS | |||
| RVTISVDTSKDQFSLKLSSVTAADTAVYYCARG | ||||
| GGQTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWTVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 283 | IGG4 | 38420 | QVQLQESGPGLVKPPETLSLTCAVSGYSISSGH | |
| HC | YWIWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GGATYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPFPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 284 | IGG4 | 38421 | QVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | |
| HC | YWFWIRQPPGKGLEWIGGIYHSGSTYYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 285 | IGG4 | 38422 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGF | |
| HC | YWTWIRQPPGKGLEWIGAIYHSGSTVYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTHTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 286 | IGG4 | 38424 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | |
| HC | YWLWIRQPPGKGLEWIGGIYHSASTAYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GTVKYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNSQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 287 | IGG4 | 38425 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGH | |
| HC | YWTWIRQPPGKGLEWIGAIYHSGSTVYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GQVTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGIHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 288 | |
38426 | QVQLQESGPGLVKPSETLSLTCAVSGYSILSGY | |
| HC | YWFWIRQPPGKGLEWIGGIYHSGSTAYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARG | ||||
| GEVTYSRGPLDVWGQGTTVTVSSASTKGPSVFP | ||||
| LAPCSRSTSFSTAALGCLVKDYFPEPVTVSWNS | ||||
| GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL | ||||
| GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPC | ||||
| PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV | ||||
| VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ | ||||
| FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL | ||||
| PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN | ||||
| QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT | ||||
| PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV | ||||
| MHEALHNHYTQKSLSLSPGK | ||||
| 289 | IGG4 | 37323 | EVQLLESGGGLVQPGGSLRLSCAASGFTFDNYA | |
| HC | MHWVRQAPGKCLEWVSAISARAGITYYADSVKG | |||
| RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARR | ||||
| IGYSYGTAPPFDVWGQGTTVTVSSASTKGPSVF | ||||
| PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN | ||||
| SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS | ||||
| LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPP | ||||
| CPAPEFLGGPSVFLPPPKPKDTLMISRTPEVTC | ||||
| VVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREE | ||||
| QFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKG | ||||
| LPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 290 | IGG4 | 38389 | QVQLVESGGGLVQPGGSLRLSCAASGFTFSDYY | |
| HC | MSWIRQAPGKGLEWVSYIASSGSVIYYADSVKG | |||
| RFTISRDNAKNSLYLQNMSLRAEDTAVYYCARH | ||||
| GTPRAFDIWGQGTTVTVSSASTKGPSVFPLAPC | ||||
| SRSTSESTAALGCLVKDYFPEPVTVSWNSGALT | ||||
| SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKT | ||||
| YTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPE | ||||
| FLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV | ||||
| SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST | ||||
| YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSI | ||||
| EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSL | ||||
| TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL | ||||
| DSDGSFFLYSRLTVDKSRWQESNVFSCSVMHEA | ||||
| LHNHYTQKSLSLSPGK | ||||
| 291 | IGG4 | 38358 | EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSA | |
| HC | MAWVRQAPGKGLEWVSTISGSCITTWYADSVKG | |||
| RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKG | ||||
| SRHLNAFNRWGQGTTVTVSSASTKGPSVFPLAP | ||||
| CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL | ||||
| TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK | ||||
| TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP | ||||
| EFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD | ||||
| VSQEDPEVQFNWYVDGVEVHHAKTKPREEQFNS | ||||
| TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSS | ||||
| IEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS | ||||
| LTCLVKCFYPSDIAVEWESNGQPENNYKTTPPV | ||||
| LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE | ||||
| ALHNHYTQKSLSLSPGK | ||||
| 292 | IGG4 | 33303 | QVQLQESGPGLVKPSGTLSLTCAVSGGSISSSN | |
| HC | WWSWVRQPPGKGLEWIGEIYHSGSTNYNPSLKS | |||
| RVTISVDKSKNQFSLKLSSVTAADTAVYYCARG | ||||
| VYHYDPYGMDVWGQGTTVTVSSASTKGPSVFPL | ||||
| APCSRSTSESTAALOCLVKDVFPEPVTVSWNSG | ||||
| ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG | ||||
| TKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCP | ||||
| APEFLGGPSVFLFPPKPKDTLMISRTPEVTCVV | ||||
| VDVSQEDPEVQFNWYVDSVEVHNAKTKPREEQF | ||||
| NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLP | ||||
| SSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ | ||||
| VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP | ||||
| PVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVM | ||||
| HEALHNHYTQKSLSLSPGK | ||||
| 293 | IGG4 | 33342 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSS | |
| HC | YYWGWIRQPPGKGLEWIGSISYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| TELGKMHFDYWGQGTLVTVSSASTKGPSVFPLA | ||||
| PCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA | ||||
| LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT | ||||
| KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA | ||||
| PEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV | ||||
| DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN | ||||
| STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPS | ||||
| SIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV | ||||
| SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP | ||||
| VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMH | ||||
| EALHNHYTQKSLSLSPGK | ||||
| 294 | IGG4 | 33329 | QLQLQESGPGLVKPSETLSLTCTVSGGSISSSD | |
| HC | YYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLK | |||
| SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR | ||||
| GSPRYMQDWGQGTLVTVSSASTKGPSVFPLAPC | ||||
| SRSTSESTAALGCLVKDYFPEPVTVSWNSGALT | ||||
| SGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKT | ||||
| YTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPE | ||||
| FLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV | ||||
| SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST | ||||
| YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSI | ||||
| EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSL | ||||
| TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL | ||||
| DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEA | ||||
| LHNHYTQKSLSLSPGK | ||||
| 295 | |
33351 | QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYY | |
| HC | MSWIRQAPGKGLEWVSYISSSGSTIYYADSVKG | |||
| RFTISRDNAKNSLYLQMNSLRAEDTAVYYCARH | ||||
| SSLGTHNWFDPWGQGTLVTVSSASTKGPSVFPL | ||||
| APCSRSTSESTAALGCLVKDYFPEPVTVSWNSG | ||||
| ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG | ||||
| TKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCP | ||||
| APEFLGGPSVFLFPPKPKDTLMISRTPEVTCVV | ||||
| VDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF | ||||
| NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLP | ||||
| SSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ | ||||
| VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP | ||||
| PVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVM | ||||
| HEALHNHYTQKSLSLSPGK | ||||
| 296 | IGG4 | 33357 | QVQLQESGPGLVKPSETLSLTCAVSGYSISSGY | |
| HC | YWGWIRQPPGKGLEWIGSIYHSGSTYYNPSLKS | |||
| RVTISVDTSKNQFSLKLSSVTAADTAVYYCARE | ||||
| GALSYSWLAAFDIWGQGTMVTVSSASTKGPSVF | ||||
| PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN | ||||
| SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS | ||||
| LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPP | ||||
| CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTC | ||||
| VVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREE | ||||
| QFNSTYRVVSVDTVLHQDWLNGKEYKCKVSNKG | ||||
| LPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK | ||||
| NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT | ||||
| TPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCS | ||||
| VMHEALHNHYTQKSLSLSPGK | ||||
| 297 | ||||
| 298 | ||||
| 299 | ||||
| 300 | LC | 33343 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLKNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 301 | LC | 37268 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKEKVYACEVT | ||||
| HQGLSSPVTKSFNRCEC | ||||
| 302 | LC | 37269 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 303 | LC | 37271 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 304 | LC | 37272 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 305 | LC | 37277 | EIVLTQSPGTLSLSPGFRATLSCGASQSVSSDY | |
| LAWYQQKPGQAPRLLIYGAYSLATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQWAVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 306 | LC | 38373 | EIVLTQSPGTLSLSPGERATLSCQASQAVSSNY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 307 | LC | 38375 | EIVLTQSPGTLSLSPGERATLSCGASQSVSSAF | |
| LAWYQQKPGQAPRLLIYGASARATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 308 | LC | 38379 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSTY | |
| LAWYQQKPGQAPRLLIYGASSREAGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQTVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 309 | LC | 38381 | EIVLTQSPGTLSLSPGERATLSCQASQAVSSNY | |
| LAWYQQKPGQAPRLLIYGASNRAAGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAIHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 310 | LC | 38383 | EIVLTQSPGTLSLSPGERATLSCQASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASNRAAGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 311 | LC | 38386 | EIVLTQSPGTLSLSPGERATLSCKASQAVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRQDGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYGQQVVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 312 | LC | 37273 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQAVHSPYTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 313 | LC | 33361 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSSYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 314 | LC | 35624 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISPLEPEDFAVYYCQQHSSYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 315 | |
38410 | EIVLTQSPGTLSLSPGERATLSCEASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASNPATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 316 | LC | 38418 | EIVLTQSPGTLSLSPGERATLSCEASQSVSASY | |
| LAWYQQKPGQAPRLLIYDASSRASGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQFSSYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 317 | |
38420 | EIVLTQSPGTLSLSPGERATLSCEASQSVSSAY | |
| LAWYQQKPGQAPRLLIYDASTRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVSSYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 318 | |
38421 | EIVLTQSPGTLSLSPGERAALSCRVSQSVSDAY | |
| LAWYQQKPGQAPRLLIYDASSRASGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVSSYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 319 | |
38422 | EIVLTQSPGTLSLSPGERATLSCEVSQSVSASY | |
| LAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 320 | |
38424 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSAY | |
| LAWYQQKPGQAPRLLIYGASDRANGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 321 | |
38425 | EIVLTQSPGTLSLSPGERATLSCRASNAVSSSY | |
| LAWYQQKPGQAPRLLIYGASDRANGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSIYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 322 | LC | 38426 | EIVLTQSPGTLSLSPGERATLSCRASNAVSSSY | |
| LAWYQQKPGQAPRLLIYGASYRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQHSLYPPTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 323 | LC | 37323 | DIQMTQSPSTLSASVGDRVTITCRASQSINSWL | |
| AWYQQKPGKAPKLLISDASSLESGVPSRFSGSG | ||||
| SGTEFTLTISSLQPDDFATYYCQQYDSHITFGG | ||||
| GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVV | ||||
| CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ | ||||
| DSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ | ||||
| GLSSPVTKSFNRGEC | ||||
| 324 | LC | 38389 | DIQMTQSPSSVSASVGDRVTITCAASQGISSDL | |
| AWYQQKPGKAPKLLIYSASSTQSGVPSRFSGSG | ||||
| SGTDFTLTISSLQPEDFATYYCQQAYLYPITFG | ||||
| GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV | ||||
| VCLLNNFYPREAKVQWKVDNALQSGNSQESVTE | ||||
| QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH | ||||
| QGLSSPVTKSFNRGEC | ||||
| 325 | LC | 38358 | GVQMTQSPSSLSASVGDRVTITCRASQDISTYL | |
| NWYQQKPGKAPKLLIYDAFNLETGVPSRFSGSG | ||||
| SGTDFTFTISSLQPEDIATYYCQQLPFLPITFG | ||||
| GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV | ||||
| VCLLNNFYPREAKVQWKVDNALQSGNSQESVTE | ||||
| QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH | ||||
| QGLSSPVTKSFNRGEC | ||||
| 326 | LC | 33303 | DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSN | |
| GYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDR | ||||
| FSGSGSGTDFTLKISRVEAEDVGVYYCMQALGG | ||||
| PWTFGGSTKVEIKRTVAAPSVFIFPPSDEQLKS | ||||
| GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQ | ||||
| ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA | ||||
| CEVTHQGLSSPVTKSFNRGEC | ||||
| 327 | LC | 33342 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASRRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQYVSDPITF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 328 | LC | 33299 | EIVLTQSPGTLSLSPGERATLSCRASQSVSSSY | |
| LAWYQQKPGQAPRLLIYGASRRATGIPDRFSGS | ||||
| GSGTDFTLTISRLEPEDFAVYYCQQVGSSPITF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 329 | |
33351 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYL | |
| NWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSG | ||||
| SGTDFTLTISSLQPEDFATYYCQQSHLVPRTFG | ||||
| GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV | ||||
| VCLLNNFYPREAKVQWKVDNALQSGNSQESVTE | ||||
| QDSKDSTYSLSSTLTLSKADYEKHKVYACFVTH | ||||
| QGLSSPVTKSFNRGEC | ||||
| 330 | |
33357 | EIVMTQSPATLSVSPGERATLSCRASQSVSSNL | |
| AWYQQKPGQAPRLLIYGASTRATGIPARFSGSG | ||||
| SGTEFTLTISSLQSEDFAVYYCQQANHHPPFTF | ||||
| GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS | ||||
| VVCLLNNFYPREAKVQWKVDNALQSGNSQESVT | ||||
| EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT | ||||
| HQGLSSPVTKSFNRGEC | ||||
| 331 | ||||
| 332 | ||||
| 333 | ||||
| 334 | Fc | ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF | ||
| for | PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS | |||
| IGG1 | SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVE | |||
| PKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKD | ||||
| TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV | ||||
| EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN | ||||
| GKEYKCKVSNKALPAPIEKTISKAKGQPREPQV | ||||
| YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW | ||||
| ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK | ||||
| SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | ||||
| 335 | Fc | ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF | ||
| re- | PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS | |||
| gion | SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVE | |||
| for | SKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLM | |||
| IGG4 | ISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVH | |||
| NAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKE | ||||
| YKCKVSNKGLPSSIEKTISKAKGQPREPQVYTL | ||||
| PPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN | ||||
| GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW | ||||
| QEGNVFSCSVMHEALHNHYTQKSLSLSPGK | ||||
| 336 | Kappa | RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY | ||
| re- | PREAKVQWKVDNALQSGNSQESVTEQDSKDSTY | |||
| gion | SLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT | |||
| for | KSFNRGEC | |||
| LC | ||||
| 337 | hHLA-G1 | MVVMAPRTLFLLLSGALTLTETWAGSHSMRYFS | ||
| AAVSRPGRGEPRFIAMGYVDDTQFVRFDSDSAC | ||||
| PRMEPRAPWVEQEGPEYWEEETRNTKAHAQTDR | ||||
| MNLQTLRGYYNQSEASSHTLQWMIGCDLGSDGR | ||||
| LLRGYEQYAYDGKDYLALNEDLRSWTAADTAAQ | ||||
| ISKRKCEAANVAEQRRAYLEGTCVEWLHRYLEN | ||||
| GKEMLQRADPPKTHVTHHPVFDYEATLRCWALG | ||||
| FYPAEIILTWQRDGEDQTQDVELVETRPAGDGT | ||||
| FQKWAAVVVPSGEEQRYTCHVQHEGLPEPLMLR | ||||
| WKQSSLPTIPIMGIVAGLVVLAAVVTGAAVAAV | ||||
| LWRKKSSD | ||||
| 338 | hHLA-G5 | MVVMAPRTLFLLLSGALTLTETWAGSHSMRYFS | ||
| AAVSRPGRGEPRFIAMGYVDDTQFVRFDSDSAC | ||||
| PRMEPRAPWVEQEGPEYWEEETRNTKAHAQTDR | ||||
| MNLQTLRGYYNQSEASSHTLQWMIGCDLGSDGR | ||||
| LLRGYEQYAYDGKDYLALNEDLRSWTAADTAAQ | ||||
| ISKRKCEAANVAEQRRAYLEGTCVEWLHRYLEN | ||||
| GKEMLQRADPPKTHVTHHPVFDYEATLRCWALG | ||||
| FYPAEIILTWQRDGEDQTQDVELVETRPAGDGT | ||||
| FQKWAAVVVPSGEEQRYTCHVQHEGLPEPLMLR | ||||
| WSKEGDGGIMSVRESRSLSEDL | ||||
| 339 | Cyno | MAVMAPRTLLLVLSGVLALTQPRAGSHSMRYFY | ||
| HLA-AG | TAVSRPGRGQPRFIAVGYVDDTQFVRFDSDAES | |||
| PRMEPRAPWVEQEGPEYWDRETQNMKTATQTYQ | ||||
| ANLRTLLRYYNQSEAGSHTFQKMYGCDLGPDGR | ||||
| LLRGYEQFAYDGRDYIILNEDLRSWTAADMAAQ | ||||
| NTQRKWEAAGAAEQHRTYLEGECLEWLRRYLEN | ||||
| GKETLQRADPPKTNVTHHPVSDYEATLRCWALG | ||||
| FYPAEITLTWQRDGEEQTEDTELVETRPTGDGT | ||||
| FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR | ||||
| WEPSSQSTILIVGIIAGLVLLGTVVTGAVVAAV | ||||
| MWRRKS | ||||
| 340 | Rhesus | MAVMAPRTLLLVLSGVLALTQTRAGSHSMRYFY | ||
| HLA-AG | TSMSRPGRGQPRFIAVGYVDDTQFVRFDSDAES | |||
| PRMEPRAPWVEQEGPEYWDRETQNMKTATQTYR | ||||
| ENLRTLLRYYNQSEAGSHTIQKMYGCDLHPFGR | ||||
| LLRGYEQFAYDGRDYIALNEDLRSWTAADMAAQ | ||||
| FTQRKWEAAGAAEQHRTYLEGECLEWLRRYLEN | ||||
| GKETLQRADPPKTNVTHHPVSDYEATLRCWALG | ||||
| FYPAEITLTWQRDGEEQTEDTETVETRPTGDGT | ||||
| FQKWAAVVVPSGEEQRYTCHVQHEGLPEPLTLR | ||||
| WEPSSQSTILIVGIIAGLVLLGTVVTGAVVAAV | ||||
| MWRRKSSDR | ||||
| 341 | hHLA- | MVVMAPRTLFLLLSGALTLTETWAGSHSMRYFS | ||
| G ECD | AAVSRPGRGEPRFIAMGYVDDTQFVRFDSDSAC | |||
| with | PRMEPRAPWVEQEGPEYWEEETRNTKAHAQTDR | |||
| signal | MNLQTLRGYYNQSEASSHTLQWMIGCDLGSDGR | |||
| peptide | LLRGYEQYAYDGKDYLALNEDLRSWTAADTAAQ | |||
| ISKRKCEAANVAEQRRAYLEGTCVEWLHRYLEN | ||||
| GKEMLQRADPPKTHVTHHPVFDYEATLRCWALG | ||||
| FYPAEIILTWQRDGEDQTQDVELVETRPAGDGT | ||||
| FQKWAAVVVPSGEEQRYTCHVQHEGLPEPLMLR | ||||
| W | ||||
| 342 | hHLA- | GSHSMRYFSPAVSRPGRGEPRFIAMGYVDDTQF | ||
| G ECD | VRFDSDSACPRMEPRAPWVEQEGPEYWEEETRN | |||
| without | TKAHAQTDRMNLQTLRGYYNQSEASSHTLQWMI | |||
| signal | GCDLGSDGRLLRGYEQYAYDGKDYLALNEDLRS | |||
| peptide | WTAADTAAQISKRKCEAANVAEQRRAYLEGTCV | |||
| EWLHRYLENGKEMLQRADPPKTHVTHHPVFDYE | ||||
| ATLRCWALGFYPAEIILTWQRDGEDQTQDVELV | ||||
| ETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHE | ||||
| GLPEPLMLRW | ||||
Claims (10)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16/584,421 US11208487B2 (en) | 2018-09-27 | 2019-09-26 | Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies |
| US17/530,072 US12264199B2 (en) | 2018-09-27 | 2021-11-18 | Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies |
| US19/065,819 US20250353913A1 (en) | 2018-09-27 | 2025-02-27 | Anti-hla-g antibodies, compositions comprising anti-hla-g antibodies and methods of using anti-hla-g antibodies |
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|---|---|---|---|
| US201862737666P | 2018-09-27 | 2018-09-27 | |
| US16/584,421 US11208487B2 (en) | 2018-09-27 | 2019-09-26 | Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies |
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| US17/530,072 Division US12264199B2 (en) | 2018-09-27 | 2021-11-18 | Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies |
| US17/530,072 Continuation US12264199B2 (en) | 2018-09-27 | 2021-11-18 | Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies |
| US19/065,819 Continuation US20250353913A1 (en) | 2018-09-27 | 2025-02-27 | Anti-hla-g antibodies, compositions comprising anti-hla-g antibodies and methods of using anti-hla-g antibodies |
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| US20200102390A1 US20200102390A1 (en) | 2020-04-02 |
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| US16/584,421 Active 2040-01-20 US11208487B2 (en) | 2018-09-27 | 2019-09-26 | Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies |
| US17/280,755 Abandoned US20210340259A1 (en) | 2018-09-27 | 2019-09-26 | Anti-hla-g antibodies, compositions comprising anti-hla-g antibodies and methods of using anti-hla-g antibodies |
| US17/530,072 Active 2041-07-26 US12264199B2 (en) | 2018-09-27 | 2021-11-18 | Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies |
| US19/065,819 Pending US20250353913A1 (en) | 2018-09-27 | 2025-02-27 | Anti-hla-g antibodies, compositions comprising anti-hla-g antibodies and methods of using anti-hla-g antibodies |
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